Tag: genetics

Happy genes love to eat

 Special people with special genes are always happy and love to eat. We are also influence by our environment but our genes is our master control until we harmed our genes from forces in the environment, prenatal nutrition , stress and other factors.

Connie

UC biologists find link between paternal diet and offspring’s health

UC biologists find link between paternal diet and offspring’s health

Doctors long have stressed the importance of good nutrition for expectant mothers.

Now biologists at the University of Cincinnati say the father’s diet could play a similar role in the health of a baby.

UC biology professors Michal Polak and Joshua Benoit manipulated the nutrition of male fruit flies and observed a strong correlation between poor diet and poor survivorship among their offspring. The study was published this week in the journal Proceedings of the Royal Society B.

“We were really surprised,” Polak said. “In many species, the moms do a lot of the care. So we expect there to be an effect from maternal diet on offspring because of that strong link. But it was a real surprise to find a link between paternal diet and offspring.”

UC collaborated on the study with researchers from the University of Western Australia and the University of Sydney’s Charles Perkins Centre.

Everyone knows a father is responsible for half of his offspring’s genes. But the UC study comes at a time when researchers are learning more about other influences fathers have on their offspring’s health that are not necessarily coded within genes, a concept called epigenetics. These influences include direct environmental effects such as exposure to toxins that can be passed from the father to his offspring through his seminal plasma.

Epigenetics is the way by which cells read genes, making some dormant and others active. Environmental cues can turn certain genes on or off. And these epigenetic modifications, too, can be inherited.

For example, an Australian study in 2016 found that male mice that lived on the equivalent of a fast-food diet were more likely to have sons that were diabetic even though daughters remained unaffected. If these traits were coded in the father’s DNA, both sons and daughters would see similar health effects.

“Epigenetic changes are seen in population genetics as less durable than actual mutations to the genetic code or DNA molecule,” Polak said. “If it’s a dominant, deleterious mutation, it could be quickly eliminated out of a gene pool by selection. But if it’s positively selected, then it could sweep the gene pool and increase in frequency until it becomes fixed.”

Research on fruit flies has earned six Nobel Prizes, including this year’s winner in physiology or medicine. The latest Nobel Prize study examined how genes control body clocks or circadian rhythms, which can help explain why some people have chronic trouble sleeping.

“I am very pleased for the field. I am very pleased for the fruit fly,” co-winner Michael Rosbash told The Associated Press.

Fruit flies are found around the world. UC’s Benoit even saw them buzzing around inside a research station in Antarctica, where they probably stowed away on food supplies imported from Chile.

The flies became popular study subjects in the early 1900s when biologists began to unravel how genetic inheritance worked. High school biology textbooks still use the color of fruit fly eyes to illustrate the concept.

Today, scientists regularly study fruit flies because they share 60 percent of our genes and more than 75 percent of our disease genes. Geneticists have mapped their entire genome. More than 150 years of study have made this unassuming little fly a good model system, Polak said.

“It’s almost arbitrary why fruit flies were chosen,” Polak said. “It just became the workhorse in those original labs.”

Benoit said flies are a practical and inexpensive test subject.

“They reproduce quickly. You can rear a few hundred in just one of these little jars. You can have thousands of fruit flies in the same amount of space you could fit six mice,” Benoit said. “It’s a great system to work on. That’s why so many questions have been answered about them.”

For the UC study, Polak isolated females and males of the fruit fly species Drosophila melanogaster, which is famous for its enormous red eyes and high reproductive capacity. A single fly can lay 50 eggs per day or as many as 2,000 eggs in her short two-month lifetime.

UC researchers fed females the same diet. But they fed males 30 different diets of yeast and sugars. The flies could eat all they wanted from the agar mixture in the bottom of their glass beaker homes, but the quality of the food varied dramatically from low to high concentrations of proteins, carbohydrates and calories.

 

After 17 days on the strict diet, the males were mated individually and consecutively with two females, which all received the same diet of yeasted cornmeal. By controlling the diet and age of the mated female, researchers tried to limit variation in maternal conditions for the study.

And by mating the males consecutively, researchers wanted to learn about the effect of male mating order and what role diet played in changing the male’s ejaculate.

After the first mating, the male fly was mated 15 minutes later with a second female. Afterward, the females were placed in isolated breeding vials filled with grape agar suitable for laying eggs. After 24 hours, researchers counted their eggs.

After another 24-hour incubation period, the eggs were examined under a microscope to determine how many hatched or contained viable embryos. Unfertilized eggs were removed from consideration. After the first count, researchers waited another 24 hours to give potentially unviable eggs time to develop or hatch but none did.

Polak and Benoit found that embryos from the second mating were more likely to survive as their fathers’ diets improved in nutrition. These effects were less apparent in the first mating. Likewise, embryo mortality was highest for offspring of males that fed on a high-carbohydrate, low-protein diet.

Researchers also found a connection between the male’s body condition and his offspring’s mortality. Males with lower energy reserves (measured in whole-body fatty acids, glucose and protein) were more likely to have fewer surviving offspring.

Females laid roughly the same number of eggs regardless of the male’s diet or mating frequency. But the study suggested that something important in the male’s ejaculate was lost between the first and second pairings.

“The second copulation is where the effects of diet really became stronger,” Polak said. “Emaciated males in poor condition produced embryos with a higher rate of mortality. But only in the second copulation.”

Polak’s study also found a slightly higher incidence of embryo mortality associated with male flies in the first mating that were fed the highest-calorie diet.

“There have been a fair number of studies that suggest male nutrition does affect reproductive capacity,” Benoit said. “But the reduction in viability was a lot smaller than what we saw in the low-quality diet or may have been masked since only a single mating was assessed.”

Polak said the study raises questions about how nutrition might affect successive generations. A 2002 Swedish population study found a correlation between 9-year-old children who had ample access to food and higher rates of diabetes and heart disease among their grandchildren. Meanwhile, children who faced privation from famine at the same age had children and grandchildren with less incidences of heart disease and diabetes.

The study was funded in part by a four-year $882,000 grant from the National Science Foundation.

Now Benoit and Polak are turning their attention to a new study examining the genetic and epigenetic responses of fruit flies that are stressed by parasitic mites.

“The seminal fluid does have a protective role to play for the embryo. You definitely have implications for embryo health and viability. But that’s another chapter,” Polak said.

The researchers also are interested in testing whether parasitic infection could change the quality of male seminal plasma, possibly exerting effects on the embryo as they observed in the diet study.

After spending most of his academic career studying them, Polak has respect for the lowly fruit fly.

“You get a special sort of appreciation for them when you see them in your kitchen courting on a piece of fruit,” he said. “You know a lot about them – and maybe you’re a little less likely to swat them.”

Source:
http://magazine.uc.edu/editors_picks/recent_features/fruitfly.html
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Connie’s comments: Whole foods, exercise, avoidance of toxins and quality supplementation are important for both mother and father to have healthy offspring.

There supplements , AGELOC  family , are also in PDRs, Physician Desk Reference and formulated at right quantity (eye formula for example is best for those with genetic predisposition to eye health issues):

http://www.clubalthea.pxproducts.com

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Hemochromatosis patients should be on a low-iron diet

HEMAHemochromatosis is a common genetic condition and yet there are still a number of misperceptions surrounding the diagnosis and management of this condition. Hemochromatosis affects both men and women. Typical patients do not have alcoholism or viral hepatitis, and often have normal liver enzymes. Clinical expression is highly variable. Genetic testing is widely available and particularly useful in family studies. Hemochromatosis can be readily diagnosed and treated. The purpose of the present review is to address the medical myths and misconceptions of hemochromatosis.

Keywords: Genetic testing, Hemochromatosis, Iron

The medical landscape is vast with an expanding array of information about old and new diseases. Thus, it becomes an insurmountable task for any physician to be up-to-date on all of the recent developments in modern medicine. For most physicians, it is acceptable to inform patients that they may not have all of the current information about their medical condition. This may lead to further study in textbooks or increasingly on the Internet, or they may seek a referral to a specialist with expertise in this area. In the present review, some of the common myths and misconceptions of hemochromatosis are explored.

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HEMOCHROMATOSIS MYTHS

Hemochromatosis is rare

A large population study (1) has demonstrated that one in 227 Caucasians in North America is homozygous for the C282Y mutation of the hemochromatosis gene. This is the typical genetic pattern seen in over 90% of typical patients; however, there are many C282Y homozygotes who are asymptomatic. Approximately, 20% of male homozygotes and 50% of female homozygotes will have normal serum ferritin levels. If the disease is defined based on symptoms, the prevalence would be much lower, and because the symptoms may be non-specific, it is more difficult to assess the prevalence of symptomatic hemochromatosis. This differs significantly between referred patients and participants in population screening studies. There has also been considerable debate about whether the genotype should be used to define hemochromatosis or whether it should be based on the presence of iron overload, independent of genotype (2). The bottom line is that this condition is extremely common within the Caucasian population and physicians should have a low index of suspicion when ordering screening tests, such as the transferrin saturation test and the serum ferritin test, for iron overload.

Women are not affected by hemochromatosis

As an autosomal recessive condition, hemochromatosis affects men and women equally in regard to the inheritance of the hemochromatosis gene. It has been considered that the effects of menses and pregnancy will significantly offset the lifelong accumulation of iron with tissue injury. A study (3) of 176 female hemochromatosis patients, matched to 176 male patients with respect to birth year, demonstrated similar hepatic iron concentrations in both sexes. However, male patients had a higher prevalence of cirrhosis compared with female patients (26% versus 14%). Cirrhosis in a female hemochromatosis patient has rarely been discovered in a population screening study. It is also important to assess women so that genetic counselling can be provided to their children and siblings.

Most hemochromatosis patients are alcoholics

The misconception that most hemochromatosis patients are alcoholics stems from the fact that most alcoholics have elevations in serum ferritin levels and some patients with alcoholic liver disease have increased iron deposition in the liver (alcoholic siderosis). This latter condition was widely reported from the Boston area in the 1960s (4) and likely ‘contaminated’ the hemochromatosis literature with patients who did not actually have genetic hemochromatosis. Studies (5,6) on the prevalence of alcoholism based on hemochromatosis pedigrees have shown no increased evidence of alcoholism. The genetic test for hemochromatosis remains a powerful diagnostic tool to help separate alcoholic liver disease from hemochromatosis.

Many hemochromatosis patients have chronic viral hepatitis

The prevalence of both hepatitis B virus (HBV) and hepatitis C virus (HCV) is not consistently higher in hemochromatosis patients. A screening study (7) that identified 302 C282Y homozygotes found one case of concomitant HCV and none with HBV. Much like alcoholic liver disease, both chronic HBV and HCV have been associated with elevations in serum ferritin levels and less commonly associated with increases in hepatic iron concentrations with advanced liver disease (8). Genetic testing is useful in this setting to differentiate hemochromatosis from iron abnormalities secondary to chronic viral hepatitis.

Diabetes is a cardinal feature of hemochromatosis

Although hemochromatosis was once called ‘bronze diabetes’, recent population screening studies (1,9) have not demonstrated an increased prevalence of diabetes in C282Y homozygotes compared with a control population. The pathogenesis of diabetes in hemochromatosis is likely multifactorial and can include defects in insulin secretion and insulin resistance (10,11).

Most hemochromatosis patients have elevated liver enzymes

Although liver disease is the most consistent feature of the disease, hemochromatosis is not an inflammatory liver disease and, therefore, many patients will have normal liver enzymes (12). In a review (13) of 351 C282Y homozygotes from our hemochromatosis clinic at the London Health Sciences Centre in London, Ontario, 277 of 351 (79%) patients had an aspartate aminotransferase level of less than 40 U/L and 238 of 351 (68%) patients had an alanine aminotransferase level of less than 40 U/L. It remains prudent to screen patients with unexplained enzyme elevations with transferrin saturation and serum ferritin tests.

Most patients with an elevated serum ferritin level have hemochromatosis

A population screening study (1) has demonstrated that elevation in serum ferritin levels is seen in approximately 10% of primary care patients. When these patients are investigated in a referral clinic, only 33% to 42% have genetic hemochromatosis. More common causes of increased serum ferritin levels include obesity, fatty liver and daily alcohol consumption (14).

An elevated hemoglobin is common in hemochromatosis

Some physicians have told patients that they do not have hemochromatosis because their hemoglobin levels are normal. Perhaps this is based on the concept that if iron deficiency reduces hemoglobin, iron excess could increase hemoglobin. A review of 634 C282Y homozygotes at our clinic at the London Health Sciences Centre (London, Ontario) showed a mean hemoglobin level of 145±13 g/L, which suggests that polycythemia is not a reliable marker for iron overload.

Hemochromatosis is not a cause of significant liver disease

It has been well established that with timely diagnosis and institution of iron depletion therapy, patients with hemochromatosis can be expected to have a prognosis equal to that of controls. However, among patients with severe iron accumulation, the risk of progression to cirrhosis is significant. As in other causes of cirrhosis, morbidity and mortality rates are increased due to the many associated complications of end-stage liver disease including the development of hepatocellular carcinoma. However, in the case of cirrhosis due to hemochromatosis, the incidence of hepatocellular carcinoma is significantly higher than that of many other causes of liver disease. Iron overload in hemochromatosis has also been shown to potentiate alcoholic liver disease and may have a similar effect on the course of HCV and nonalcoholic fatty liver disease (15–17). Given that 1.8% of the population in the United States are HCV-positive and that up to 24% have nonalcoholic fatty liver disease, the coexistence of these disorders with hemochromatosis is likely to affect a reasonable proportion of our population.

Carriers of the hemochromatosis gene often have iron overload

It has been common for physicians to tell patients with mild elevations in serum ferritin levels that they may be carriers of the hemochromatosis gene. Mild elevations in serum ferritin levels in the general population are very common and occur in all ethnic groups, so they are unlikely to be explained on the basis of heterozygosity for the hemochromatosis gene. A large population study (1) has now demonstrated that C282Y heterozygotes have iron studies similar to those of the general population. There is an increased prevalence of mild iron overload in compound heterozygotes (C282Y/H63D), and some C282Y heterozygotes may also carry an unidentified second mutation.

Children of hemochromatosis patients are at the highest risk of disease

The misconception that children of hemochromatosis patients are at the highest risk of disease arises because of a misunderstanding by patients and physicians of the concept of autosomal recessive inheritance. Usually a typical C282Y homozygote has heterozygous parents and so there is a higher risk for siblings. The risk is slightly higher than 25% because there is a possibility that one of the parents is a homozygote. Children of homozygotes are at a much lower risk because the partner must also carry the C282Y mutation. Among Caucasian couples, the risk to children is approximately 5% (18). Genetic testing of children younger than 18 years of age is not recommended because of a number of potential concerns about informed consent and genetic discrimination.

Genetic testing for hemochromatosis is a research tool

Genetic testing for hemochromatosis has a number of unique characteristics. Unlike most genetic diseases, in hemochromatosis there is a single genetic mutation (C282Y) that explains most typical cases. The test is widely available and can be performed at a relatively low cost. There have been a number of studies (19–21) that have assessed the psychosocial impact of genetic testing for hemochromatosis which have concluded that the test is well accepted by patients and has rarely been associated with insurance discrimination. For these reasons, the genetic test has become one of the most commonly requested tests and is a powerful diagnostic tool that is accessible to most physicians.

Hemochromatosis patients should be on a low-iron diet

Although dietary iron is the source of excess iron in hemochromatosis, a decrease in dietary iron has not been shown to decrease iron stores in hemochromatosis. All food groups contain iron and most humans will absorb only a small fraction of orally ingested iron. Iron absorption includes components from heme and nonheme iron sources (22), and the control or lack of control over these regulatory mechanisms is incompletely understood in hemochromatosis. It has been speculated that a defect in hepcidin, a circulating peptide produced by the liver, is a fundamental defect in hemochromatosis which results in an increase in intestinal iron absorption (23). Iron supplementation of food was introduced in the 1950s as a marketing tool, and the added iron has poor bioavailability. Generally, vegetarians have lower serum ferritin levels than meat-eating patients but this does not translate into a dietary recommendation (24). The description of bacterial infections from Yersinia (25) and other Vibrio species has led to recommendations to avoid raw shellfish which may be appropriate for all patients rather than just hemochromatosis patients. Hemochromatosis patients are advised to avoid iron supplementation and large doses of supplemental oral vitamin C which may adversely affect some patients with iron overload (26).

Hemochromatosis is a progressive disease

Because hemochromatosis patients presumably begin absorbing excess iron at birth, it seems intuitive that progressive iron overload over time would occur. However, it has not been possible to show a correlation between liver iron concentration and age in hemochromatosis (27). It has become apparent through various studies, in which genetic testing was performed after many years of observation such as in the Copenhagen Heart Study (28), that many C282Y homozygotes do not have a progressive rise in serum ferritin levels, even without phlebotomy treatment. This is the most likely explanation for the discordance between the high frequency of the hemochromatosis genotype and the relatively low representation of hemochromatosis in liver transplant registries (29) or in death certificate data (30). There have been patients who have refused phlebotomy therapy and have been observed over many years to not have any changes in their serum ferritin levels. Phlebotomy therapy has never been subjected to a randomized trial. The strongest supporting evidence for a beneficial effect of phlebotomy is the improvement of liver fibrosis that has been demonstrated on serial liver biopsies in hemochromatosis patients (31). Maintenance therapy is even less established following iron depletion, and many patients will not demonstrate any evidence of iron reaccumulation after many years of observation (32). Many patients enjoy the concept of continuous therapy for hemochromatosis and these patients can be encouraged to be voluntary blood donors several times per year (33). If they are ineligible, an annual ferritin determination is a reasonable alternative to guide maintenance therapy.

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SUMMARY

Hemochromatosis is a common and relatively simple genetic disease to diagnose and treat. It can be diagnosed and treated by family physicians using transferrin saturation, serum ferritin and C282Y genetic testing. Physicians who are not comfortable with interpretation of the genetic test and subsequent family counselling should refer to local specialists and try to avoid any perpetration of misinformation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657669/

Connie’s comments: Calcium and magnesium supplements cancels iron absorption.

Gender bias in treating or preventing blood clots in women

Animation of the formation of an occlusive thrombus in a vein. A few platelets attach themselves to the valve lips, constricting the opening and causing more platelets and red blood cells to aggregate and coagulate. Coagulation of unmoving blood on both sides of the blockage may propagate a clot in both directions.

A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut off (termed an occlusive thrombus), resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is considered an embolus.

Some of the conditions which elevate risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity (see deep venous thrombosis), and genetic or disease-related deficiencies in the blood’s clotting abilities.

Formation

Platelet activation can occur through different mechanisms such as a vessel wall breach that exposes collagen, or tissue factor encryption.[clarification needed] The platelet activation causes a cascade of further platelet activation, eventually causing the formation of the thrombus.[2]This process is regulated through thromboregulation.

  • Illustration Comparing Normal Artery vs Diseased Artery with a Blood Clot

  • Micrograph showing a thrombus (center of image) within a blood vessel of the placenta. H&E stain.

  • Illustration depicting thrombus formation over arterial plaque.

Prevention and treatment

Main articles: Thrombolysis, Thrombosis prophylaxis, and Reperfusion therapy

Blood clot prevention and treatment reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing thrombi; the former binds to and activates the enzyme inhibitor antithrombin III, while the latter inhibits vitamin K epoxide reductase, an enzyme needed to synthesize mature clotting factors.

Some treatments have been derived from bacteria. One drug is streptokinase, which is an enzyme secreted by several streptococcal bacteria. This drug is administered intravenously and can be used to dissolve blood clots in coronary vessels. However, streptokinase is nonspecific and can digest almost any protein, which can lead to many secondary problems. Another clot-dissolving enzyme that works faster and is more specific is called tissue plasminogen activator (tPA). This drug is made by transgenic bacteria and it converts plasminogen into the clot-dissolving enzyme plasmin.[3] There are also some anticoagulants that come from animals that work by dissolving fibrin. For example, Haementeria ghilianii, an Amazon leech, produces an enzyme called hementin from its salivary glands.[4] As of 2012, this enzyme has now been successfully produced by genetically engineered bacteria and administered to cardiac patients.

Prognosis

Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization.[5]

  1. Propagation of a thrombus occurs towards the direction of the heart. This means that it is anterograde in veins or retrograde in arteries.
  2. Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile. A venous embolus (mostly from deep vein thrombosis in the lower limbs) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery resulting in a pulmonary embolism. Arterial thrombosis resulting from hypertension or atherosclerosis can become mobile and the resulting emboli can occlude any artery or arteriole downstream of the thrombus formation. This means that cerebral stroke, myocardial infarction, or any other organ can be affected.
  3. Dissolution occurs when the fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by drugs (for example after occlusion of a coronary artery). The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed.
  4. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue.[citation needed]

Stroke in women

A number of factors are likely behind the surprising rise in strokes in women, including:

  • Increasing rates of obesity (women’s waists have grown by nearly two inches in the last 10 years)
  • Vitamin D3 deficiency due to lack of sun exposure. Sun avoidance also increases your risk of vitamin D sulfate deficiency, which may be an underlying cause of arterial plaque buildup (a risk factor for stroke)
  • Rising prevalence of high blood sugar levels
  • eating unprocessed, preferably organic, foods, exercising and maintaining a healthy weight will help to reduce your risk of stroke. Two additional risk factors that can have a direct impact on your stroke risk are:
    • Psychological distress. According to a 2008 study published in the journal Neurology, the more stressed you are, the greater your risk. The researchers actually found that for every notch lower a person scored on their well-being scale, their risk of stroke increased by 11 percent. Not surprisingly, the relationship between psychological distress and stroke was most pronounced when the stroke was fatal.
    • Hormone replacement therapy (HRT) and birth control pills. If you’re on one of the hormonal birth control methods (whether it’s the pill, patch, vaginal ring or implant), it is important to understand that you are taking synthetic progesterone and synthetic estrogen — something that is clearly not advantageous if you want to maintain optimal health. These contraceptives contain the same synthetic hormones as those used in hormone replacement therapy (HRT), which has well-documented risks, including an increased risk of blood clots, stroke, heart attack, and breast cancer.

Diet Soda May Dramatically Increase Your Stroke Risk

Earlier this year, research presented at the American Stroke Association’s International Stroke Conference showed that people who drink just one diet soda a day may increase their risk of stroke by 48 percent!

According to the authors:

“This study suggests that diet soda is not an optimal substitute for sugar-sweetened beverages, and may be associated with a greater risk of stroke, myocardial infarction, or vascular death than regular soda.”

While more research will likely be needed to confirm this potential link, there’s plenty of evidence showing that artificial sweeteners such as aspartame and sucralose (Splenda) can be dangerous to your health. I believe aspartame is, by far, the most dangerous artificial sweetener on the market. Reports of adverse reactions to the US FDA also support this, as aspartame accounts for over 75 percent of the adverse reactions to food additives reported to the FDA.

Embolism

An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel.[1] The embolus may be a blood clot (thrombus), a fat globule, a bubble of air or other gas (gas embolism), or foreign material. An embolism can cause partial or total blockage of blood flow in the affected vessel.[2] Such a blockage (a vascular occlusion) may affect a part of the body distant from where the embolus originated. An embolism in which the embolus is a piece of thrombus is called a thromboembolism. Thrombosis, the process of thrombus formation, often leads to thromboembolism.

An embolism is usually a pathologic event (that is, part of illness or injury). Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Such therapy is called embolization.

Gender bias in treating or preventing blood clots in women

In health care, gender disparities are especially pernicious. If you are a woman, studies have shown, you are not only less likely to receive blood clot prophylaxis, but you may also receive less intensive treatment for a heart attack. If you are a woman older than 50 who is critically ill, you are at particular risk of failing to receive lifesaving interventions. If you have knee pain, you are less likely to be referred for a knee replacement than a man, and if you have heart failure, it may take longer to get EKGs.

When Dr. Elliott Haut and his team at Johns Hopkins Hospital in Baltimore designed their blood clot prevention protocol back in 2006, they didn’t expect to discover systemic gender bias. But the data were clear and the implications were alarming: Women who were trauma patients at Johns Hopkins Hospital were in considerably greater danger of dying of preventable blood clots than men.

Why? Because doctors were less likely to provide them with the appropriate blood clot prevention treatment. At Hopkins, as at many hospitals, both men and women were receiving treatment at less than perfect rates, but while 31 percent of male trauma patients were failing to get proper clot prevention, for women, the rate was 45 percent. That means women were nearly 50 percent more likely to miss out on blood clot prevention.

Blood clots, gelatinous tangles that can travel through the body and block blood flow, kill more people every year than breast cancer, AIDS and car crashes combined. But many of these clots can be avoided — if doctors prescribe the right preventive measures.

Such implicit bias, as researchers now understand, happens when we unintentionally use stereotypes or associations to make judgments. “Perhaps we take women’s symptoms less seriously, or we interpret them as having an emotional cause as opposed to a physical cause,” said Dr. Christine Kolehmainen, the associate director for women’s health at the Middleton Memorial Veterans Hospital in Madison, Wis. Studies bear this out: in one study of patients with irritable bowel syndrome, doctors were more likely to suggest that male patients receive X-rays and more likely to offer female patients tranquilizers and lifestyle advice.

In the case of blood clot prevention, doctors’ assumptions about women’s risk factors could lead to disparities in treatment. “There might be stereotypes about women’s biology or environment or occupation that could all play into medical decision-making,” Kolehmainen said.

Whether unintentional, unconscious or simply based on erroneous assumptions, treatment differentials clearly exist. Interventions like the Hopkins checklist can help correct them.

Google Women , blood clots, birth control,  pills trauma, PTSD , pregnancy

GWS study identifies a single major locus contributing to survival into old age – the APOE locus

Apolipoprotein E (APOE) is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.[4] In peripheral tissues, APOE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. In the central nervous system, APOE is mainly produced by astrocytes, and transports cholesterol to neurons via APOE receptors, which are members of the low density lipoprotein receptor gene family.[5] APOE is the principal cholesterol carrier in the brain.[6] This protein is involved in Alzheimer’s disease and cardiovascular disease.[7]

Gene

The gene, APOE, is mapped to chromosome 19 in a cluster with Apolipoprotein C1 and the Apolipoprotein C2. The APOE gene consists of four exons and three introns, totaling 3597 base pairs. APOE is transcriptionally activated by the liver X receptor (an important regulator of cholesterol, fatty acid, and glucose homeostasis) and peroxisome proliferator-activated receptor γ, nuclear receptors that form heterodimers with Retinoid X receptors.[8] In melanocytic cells APOE gene expression may be regulated by MITF.[9]
Protein[edit]
APOE is 299 amino acids long and contains multiple amphipathic α-helices. According to crystallography studies, a hinge region connects the N- and C-terminal regions of the protein. The N-terminal region (residues 1–167) forms an anti-parallel four-helix bundle such that the non-polar sides face inside the protein. Meanwhile, the C-terminal domain (residues 206-299) contains three α-helices which form a large exposed hydrophobic surface and interact with those in the N-terminal helix bundle domain through hydrogen bonds and salt-bridges. The C-terminal region also contains a low density lipoprotein receptor (LDLR)-binding site.[10]

Polymorphisms

APOE is polymorphic,[11][12] with three major alleles: ApoE2 (cys112, cys158), ApoE3 (cys112, arg158), and ApoE4 (arg112, arg158).[7][13][14] Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,[15][16][17] these differences alter APOE structure and function. These have physiological consequences:
E2 (rs7412-T, rs429358-T) has an allele frequency of approximately 7 percent.[18] This variant of the apoprotein binds poorly to cell surface receptors while E3 and E4 bind well.[19] E2 is associated with both increased and decreased risk for atherosclerosis. Individuals with an E2/E2 combination may clear dietary fat slowly and be at greater risk for early vascular disease and the genetic disorder type III hyperlipoproteinemia—94.4% of such patients are E2/E2, while only ∼2% of E2/E2 develop the disease, so other environmental and genetic factors are likely to be involved (such as cholesterol in the diet and age).[20][21][22] E2 has also been implicated in Parkinson’s disease,[23] but this finding was not replicated in a larger population association study.[24]
E3 (rs7412-C, rs429358-T) has an allele frequency of approximately 79 percent.[18] It is considered the “neutral” Apo E genotype.
E4 (rs7412-C, rs429358-C) has an allele frequency of approximately 14 percent.[18] E4 has been implicated in atherosclerosis,[25] Alzheimer’s disease,[26][27] impaired cognitive function,[28][29] reduced hippocampal volume,[29] HIV,[30] faster disease progression in multiple sclerosis,[31][32] unfavorable outcome after traumatic brain injury,[33] ischemic cerebrovascular disease,[34] sleep apnea,[35][36] accelerated telomere shortening [37] and reduced neurite outgrowth.[38] A notable advantage of the E4 allele (relative to E2 and E3) is a positive association with higher levels of vitamin D, which may help explain its prevalence despite its seeming complicity in various diseases or disorders.

By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P < 1 × 10−4) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR = 0.71 (95% CI 0.65–0.77), P = 3.39 × 10−17]. This SNP, rs2075650, is located in TOMM40at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P = 0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found.

Introduction

Worldwide human populations have shown an increase in mean life expectancy in the past two centuries (Oeppen & Vaupel, 2002). This is mainly because of environmental factors such as improved hygiene, nutrition, and health care. The large variation in healthy lifespan among the elderly has prompted research into the determinants of aging and lifespan regulation. The genetic contribution to human lifespan variation was estimated at 25–30% in twin studies (Gudmundsson et al., 2000; Skytthe et al., 2003; Hjelmborg et al., 2006). The most prominent genetic influence is observed in families in which the capacity to attain a long lifespan clusters (Perls et al., 2000; Schoenmaker et al., 2006). Exceptional longevity can be reached with a low degree of age-related disability (Christensen et al., 2008; Terry et al., 2008), raising the question whether protective mechanisms against disease exist in long-lived subjects.

In most experimentally modified animal model systems, single-gene mutations in many different genes have major life extension effects (Fontana et al., 2010; Kenyon, 2010). However, natural human and animal longevity is presumed to be a complex trait (Finch & Tanzi, 1997). In humans, both candidate gene and genome-wide genetic association approaches have been applied in an attempt to identify longevity loci. The frequency of genetic variants has been typically compared between nonagenarian cases and young controls, revealing loci at which genetic variants may contribute to a higher or lower probability of survival into old age. The initial candidate gene studies aimed at finding human longevity genes were dominated by contradictory results (Christensen et al., 2006). The more consistent evidence obtained by repeated observation in independent cohort studies for association with longevity has so far only been observed for three loci, the apolipoprotein E (APOE) locus (Schachter et al., 1994; Christensen et al., 2006), the FOXO3A locus (Willcox et al., 2008; Flachsbart et al., 2009; Pawlikowska et al., 2009; Soerensen et al., 2010), and the AKT1 locus (Pawlikowska et al., 2009). Thus, despite the expectation that longevity would be influenced by many genetic variants with small effect sizes, the effect of variants has consistently been shown in only three genes.

Hypothesis-free genome-wide approaches have also been undertaken. Genome-wide linkage scans reported evidence for linkage with longevity on chromosome 4q25 (Puca et al., 2001), 3p24-22, 9q31-34, and 12q24 (Boyden & Kunkel, 2010). However, the evidence for these loci is still very weak as the results, obtained in centenarians and their families, could not be replicated in nonagenarian sibling pairs (Beekman et al., 2006) or have yet to be tested in other studies. A meta GWAS of survival to 90 years or older in 1836 cases and 1955 controls did not find any significant genome-wide associations (Newman et al., 2010). Thus far, hypothesis-free approaches have not identified any loci involved in longevity.

In a few studies, such as the Ashkenazi Jewish Centenarian Study and the Leiden Longevity Study (LLS), different generations of long-lived families are being investigated for parameters and pathways contributing to the longevity phenotype (Atzmon et al., 2004; Schoenmaker et al., 2006). The survival benefit of the LLS families is marked by a 30% decreased mortality risk in the survival analysis of three generations, i.e., the parents of the probands in this study (nonagenarian sibling pairs), their unselected additional siblings, and their offspring (Schoenmaker et al., 2006). As compared to their partners, the offspring of nonagenarians siblings have a lower prevalence of type 2 diabetes, myocardial infarction and hypertension (Westendorp et al., 2009), a beneficial glucose, lipid, and thyroid metabolism, and a preservation of insulin sensitivity with age (Rozing et al., 2009, 2010a,b; Vaarhorst et al., 2011; Wijsman et al., 2011). Hence, in middle age, these families display beneficial metabolic profiles.

Because the longevity phenotype is inherited in the LLS families, they offer a route to identify genetic variants that influence human longevity. Previously, we tested whether the absence of GWAS-identified alleles promoting common diseases might explain their familial longevity (Beekman et al., 2010). Longevity was not easily explained by the absence of disease-susceptibility alleles. More likely therefore, the genome of the long-lived harbors longevity-promoting alleles. To identify such loci, we performed a GWAS comparing nonagenarian siblings from the LLS and younger population controls. We subsequently investigated emerging candidate SNPs in nonagenarian cases from the Rotterdam Study, the Leiden 85-plus study, and the Danish 1905 cohort.

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Results

GWAS

A GWAS was performed in nonagenarian participants from the LLS and middle-aged controls from the Rotterdam Study (RS). Genotype data for 516,721 SNPs that passed quality control thresholds were analyzed in a comparison of 403 unrelated nonagenarians (94 years on average) and 1670 controls (58 years on average). A flow chart of the consecutive analysis steps is depicted in Fig. 1, and a description of the population samples investigated in the GWAS and subsequent replication studies is given in Table 1. Results of the association analysis of stage 1 are depicted in Fig. S1. None of the SNPs reached genome-wide significance (P < 5 × 10−8).

Table 1

Characteristics of the genotyped samples used for analysis
Fig. 1

Flow chart of experimental work.

Replication studies

We prioritized the SNPs that had the most significant association with survival into old age according to the analysis of stage 1 (P < 1 × 10−4, Table S1). For 58 of the 62 selected SNPs, successful genotyping was obtained in the replication cohorts. In stage 2, these 58 SNPs were tested for association comparing 960 RS replication cases (mean age of 93 years), 1208 Leiden 85-plus replication cases (mean age of 92 years), and 1578 Danish replication cases (mean age of 93 years) with appropriate middle-aged population controls (Table 1). Meta-analysis for the 58 SNPs, comprising a total of 4149 nonagenarian cases and 7582 younger controls (from the LLS GWAS, RS replication, Leiden 85-plus replication, and Danish replication studies), was performed.

Rs2075650 on chromosome 19 was the only SNP that was associated with survival into old age at the genome-wide significance level (P = 3.39 × 10−17) (Table S2A). The minor allele was underrepresented among the older cases as compared to middle-aged controls, hence associated with the decreased probability of carriers surviving into old age corresponding to an odds ratio (OR) below unity [OR = 0.71 (95% CI 0.65-0.77)]. This effect is observed in both sexes (Table S2B, C). The remaining 57 SNPs did not show genome-wide significant effects on longevity either in men or women (Table S2B for men and S2C for women). The association of rs2075650 with survival did show some heterogeneity across the four studies (P = 0.0495), which is mainly because of the RS.

rs2075650 and the APOE ε2/ε3/ε4 polymorphism

Rs2075650 is located in the TOMM40 gene, next to the APOE gene (Fig. S2). APOE was previously associated with longevity (Schachter et al., 1994; Christensen et al., 2006). The ApoE protein has three isoforms (ApoE ε2, ApoE ε3, and ApoE ε4) which are defined by two SNPs, rs7412 (Arg136Cys; ε2) and rs429358 (Cys112Arg; ε4). A meta-analysis of rs7412 and rs429358, in the LLS GWAS study, the Leiden 85-plus replication study, and the Danish replication study samples (3189 cases and 5757 controls), showed a significant association of rs429358 with longevity [OR = 0.62 (95% CI 0.56–0.68), P = 1.33 × 10−23], which was comparable to rs2075650 [OR = 0.67 (95% CI 0.61–0.74), P = 9.15 × 10−17]. Rs7412 also showed an association with longevity, with a higher prevalence of the minor allele in nonagenarians [OR = 1.31 (95% CI 1.17–1.46), P = 1.35 × 10−6].

Genetic variants in PVRL2-TOMM40-APOE region are associated with human longevity in a Han Chinese population.

Abstract

Human longevity results from a number of factors, including genetic background, favorable environmental, social factors and chance. In this study, we aimed to elucidate the association of human longevity with genetic variations in several major candidate genes in a Han Chinese population.

METHODS

A case-control association study of 1015 long-lived individuals (aged 90 years or older) and 1725 younger controls (30-70 years old) was undertaken. Rs2075650 in TOMM40 was firstly genotyped using the ABI SNaPshot method in an initial cohort consisted of 597 unrelated long-lived individuals and 1275 younger controls enrolled from Sichuan. Secondly, eighteen tag single-nucleotide polymorphisms (SNPs) in the PVRL2-TOMM40-APOE locus were genotyped for extensive study in the same cohort. Finally, 5 associated SNPs were genotyped in a replication cohort including 418 older individuals and 450 younger controls. The genotype and allele frequencies were evaluated using the χ2 tests. The linkage disequilibrium (LD) block structure was examined using the program Haploview.

RESULTS

The case-control study of rs2075650 in TOMM40 showed significant difference in allele frequencies between cases and controls (P = 0.006) in an initial study. Of the 18 SNPs genotyped, rs405509 in APOE and another three SNPs (rs12978931, rs519825 and rs395908) in the PVRL2 gene also showed significant association with human longevity in extensive study in the same cohort. Rs2075650 in TOMM40, rs405509 in APOE and rs519825 in PVRL2 showed a significant association with human longevity in a replication cohort.

CONCLUSION

These results suggested that PVRL2, TOMM40 and APOE might be associated with human longevity. However, further research is needed to identify the causal variants and determine which of these genes are involved in the progress of human longevity.

https://www.ncbi.nlm.nih.gov/pubmed/24924924

Association between apolipoprotein E polymorphism and Alzheimer disease in Tehran, Iran.

Abstract

Epsilon 4 allele of apolipoprotein E (APOE-epsilon4) is a major risk factor for Alzheimer’s disease (AD). The association of APOE allele frequencies with AD remains unknown in developing countries. We examined the frequency of APOE alleles in 105 patients with AD and 129 cognitively normal subjects of similar age and sex (control group), in Tehran, Iran.

The APOE-epsilon4 allele frequency was significantly higher in the AD subjects than in the control group (21% versus 6.2%, p < 0.001). In addition, the OR for APOE-epsilon4 heterozygous and homozygous subjects were 3.2 (p = 0.001) and 12.75 (p = 0.01), respectively. The OR was not uniform across age groups.

The AD subjects carrying one or two APOE-epsilon4 allele showed earlier age-at-onset (p < 0.001).

These data suggest that the APOE-epsilon4 allele increase the risk for AD in Tehran population in a dose and age-dependent manner.

Although the APOE-epsilon2 allele frequency was lower in the AD subjects than in the control group (0.95% versus 2.7%, p = 0.15), APOE-epsilon2 was not associated with the onset of AD in Tehran’s population. The OR for epsilon2 allele in AD subjects was 0.34 (p = 0.21). The genotype frequencies for epsilon3, epsilon4, and epsilon2 alleles in control subjects were 91.2, 6.1, and 2.7%, respectively. These values were similar to that reported for Turkish, Greece, Japanese, Spanish, and Moroccan populations, but they were significantly different from the reported values for the other ethnic populations.

This observation emphasizes the importance of geographical location and ethnical background of the subjects in the study of APOE genotypes and their association with AD.

https://www.ncbi.nlm.nih.gov/pubmed/15664112

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https://clubalthea.com/2016/10/14/your-complete-dna-sequence-will-help-shape-the-future-of-medicine/

Risk factors for addiction

By Maya Tyler

For both medical professionals and patients alike, it can be difficult to understand why particular people are more vulnerable to addiction than others. Often referred to as “the disease that knows no boundaries,” addiction doesn’t seem to discriminate based on color, ethnicity, height, weight, or social status. Moreover, attempting to identify the cause of addiction usually yields a complex answer. There can be numerous risk factors that may predispose a person for addictive behavior, regardless of an individual’s upbringing or moral code. While the risk factors for a drug addiction may differ than those for a sex or gambling problem, there tend to be many individual, social, and biological variables that combine to increase the chances there will be onset and progression of addiction of an individual if exposed to a substance or behavior.

Genetics

Over the course of the last few decades, science has proven that addiction is not a matter of weak willpower or moral degeneration. It appears that the chemical reactions of an addicted brain are significantly different than those of a “normal,” un-addicted brain. This explains why one person may be able to smoke cigarettes occasionally for pleasure, while another needs them on a daily basis in order to feel normal and to function properly.

 

Heredity, is a significant risk factor for addiction. In fact, scientists estimate that 40 to 60 percent of a person’s predisposition for addiction is based on genetics. In families where addiction is present, children are far more likely to have addiction problems as adults, especially if they witness a parent’s addictive behavior on a day-to- day basis.

Unfortunately, a person with the “addictive personality” may be at risk for a wide range of addictions. For example, a person with an alcoholic parent may choose not to drink, but will then become addicted to smoking or compulsive eating. Brain activity and pleasure responses in the addicted person appear to be the same, regardless of the addictive substance or behavior.

Environment

Environmental factors can also pose risks to a potential addict. For children and adolescents, lack of parental involvement or supervision can enable risky behaviors or experimentation with alcohol or drugs. Additionally, young people who experience abuse or neglect from parents may begin to use substances or engage in addictive behavior as an emotional coping mechanism.

In older adolescents and even adults, peer pressure is also a risk factor for addiction. Though it might not be overt or aggressive in nature, the pressure from friends to fit in or be accepted in a particular social circle can often create a breeding ground for addiction to take root and develop. The availability of a substance, as in the case of a college student having easy access to drugs or alcohol, may also make it much easier for an individual to become addicted.

Environmental factors can be so strong that an addict in recovery usually finds it necessary to avoid certain situations or people that may trigger a craving or a relapse into the addictive behavior.

Dual Diagnoses

In the medical community, a person with a “dual diagnosis” is someone who has an identified addiction as well as a mental health disorder, such as obsessive-compulsive disorder or depression. It’s commonly believed that an underlying mental-emotional condition can predispose a person to addiction, and that the addiction can then exacerbate the symptoms or severity of the original condition. This causes a destructive cycle in which the addiction tends to progress rapidly and with severe negative consequences.

In other cases, a medical condition might predispose a person for addiction. For example, a person who is taking prescription pain pills after a surgery might become addicted to that substance. Or, an injury or illness could drastically change a person’s lifestyle, which can encourage the use of drugs or alcohol as a coping mechanism.

Drug of Choice

While some addictions progress slowly over the course of several months or years, certain substances may pose higher risks for addiction than others. Physiologically, drugs like cocaine, heroin, and methamphetamines tend to be more physically addicting than substances like alcohol or marijuana. Since the withdrawal or “come-down” from cocaine or heroin use tends to be severely painful, the person is more likely to use the drug frequently and in higher doses, thereby significantly “speeding up” the process of addiction.

Method

Just as particular drugs may be more addictive than others, the method of use can also predispose a person for addiction. Substances that are smoked or injected into the body tend to be more addictive than those that are ingested. This is because the substance goes straight into the bloodstream and brain without being filtered by the liver and other detoxifying organs.

Early Use

Another risk factor for addiction is the age at which the use or behavior started. Research has shown that the younger the user is, the more likely he or she is to become addicted. Addictive behavior in the developing years can also have a negative impact on brain development, making young people more prone to mental-emotional disorders as the addiction progresses into their later years.

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