Saturday, February 8, 2014

common genetic variation in the gene may modify cardiovascular benefit of aspirin

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common genetic variation in the gene may modify cardiovascular benefit of aspirin -

Aspirin is the gold standard antiplatelet therapy for aspirin and low daily dose is widely prescribed for the prevention of cardiovascular disease.

Now, a new study suggests that common genetic variation in the gene for catechol-O-methyltransferase (COMT) can modify the cardiovascular benefit of aspirin, and in some people, can impart a slight evil . The results, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH) appear online in the journal American Heart Association Arteriosclerosis, Thrombosis, and Vascular Biology .

"This is one of the rare cases where you can identify a single gene polymorphism has a significant interaction with aspirin as it affects whether or not it protects against heart disease" says first author Kathryn hall, PhD, MPH, an investigator in the general medicine division and primary care at BIDMC and researcher at Harvard medical School.

COMT is a key enzyme in the metabolism of catecholamines , a group of hormones that include adrenaline, noradrenaline and dopamine. "These hormones are involved in a wide range of disorders, including hypertension," says Hall, "first, we were interested in whether the COMT gene affected the vulnerability to cardiovascular incident such as myocardial infarction or ischemic stroke. "Knowing that aspirin is commonly prescribed for the prevention of cardiovascular diseases of the incident, investigators also wanted whether genetic variation in COMT influence potential benefit of aspirin.

To answer these questions, the researchers used data from genomics women's health study, a cohort of more than 23,000 women who were followed for 10 years in a randomized controlled trial against placebo double-blind, the low-dose aspirin or vitamin E in the primary prevention of cardiovascular disease in the incident. Their analysis included val158met, a common variant in the COMT gene: People who are homozygous for valine highly active form of the enzyme, the "val / vals," have been shown to have lower levels of catecholamines compared to persons who are homozygous for methionine the low activity form of the enzyme, the "met / metastasis." the val / met are heterozygous between.

"When we looked at women in the placebo arm of the test, we found that 23 percent of women who were "val / vals' were naturally protected against cardiovascular disease incident," says lead author Daniel I. Chasman, PhD, genetic epidemiologist in the Division preventive medicine at Brigham and Women's Hospital and associate professor of medicine at Harvard medical School. "This discovery has been replicated in two other studies based on the population, was in itself a significant interest." But, he adds, the investigation also revealed the surprising discovery that when women with the Val / Val polymorphism were allocated to aspirin, this natural protection has been eliminated.

"As we continued to examine the effects of the drug benefit, we found that val / val women who were randomly assigned to aspirin had more cardiovascular events than val / vals that were assigned to placebo, "said Chasman. Of the 28 percent of women who met / met, the opposite was true, and women had fewer cardiovascular events when assigned to aspirin compared with placebo. The benefit of aspirin compared with placebo allowance encountered / Metastases raised to the reduction of cases of incident cardiovascular disease in 91 women treated over 10 years of follow-up studies. However, the harm of aspirin compared with placebo allowance for the val / val women was an increase of one case per 91 treaties.

The researchers also found that rates of cardiovascular disease were also reduced in met / met women assigned to vitamin E compared with those assigned to placebo.

the authors point out that the results will require further research and replication to understand their potential clinical impact. However, they note that, since aspirin is preventive prescribed to millions of people and the COMT gene variant is extremely common, this study highlights the potential importance of individualizing therapy based on genetic profiles.

"What this study suggests is that we can be smarter about groups of patients who would likely benefit from aspirin," says study co-author Joseph Loscalzo, MD, PhD, chair of the Department of medicine and chief physician at BWH. "Rather than give aspirin to all patients with risk factors for heart disease, we need to use genomics and modern genetics to identify persons for whom aspirin has the greatest benefit and the least risk of side effects. "

One possible reason for the val / val protection could lie in the role of COMT in the allocation of adrenaline, the hormone "fight or flight", which is closely related to the regulation of the cardiovascular system.

"When adrenaline levels increase in response to stress, blood pressure rises and blood pressure is a precursor of heart disease, "says hall. "One possibility is that individuals val val / less epinephrine that meets / met individuals because of their COMT is more efficient at decomposing This could help protect the course against cardiovascular disease. - Who is our working hypothesis It is more difficult to explain why. effect is modified by aspirin and that is what we are in the laboratory aggressively try to understand. "


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