Genetic variation may modify cardiovascular benefit of aspirin

July 21, 2014

A new study suggests that a common genetic variation in the gene for catechol-O-methyltransferase (COMT) may modify the cardiovascular benefit of aspirin, and in some people may confer slight harm. The findings appear online in Arteriosclerosis, Thrombosis, and Vascular Biology.

“This is one of the few cases where you can identify a single genetic polymorphism which has a significant interaction with aspirin such that it affects whether or not it protects against cardiovascular disease,” says first author Kathryn Hall, PhD, MPH. COMT is a key enzyme in the metabolism of catecholamines. Knowing that aspirin is commonly prescribed for the prevention of incident cardiovascular disease, the investigators wanted to learn if genetic variation in COMT would influence aspirin's potential benefit.

The researchers used data from the Women's Genome Health Study, a cohort of more than 23,000 women who were followed for 10 years in a randomized double-blind, placebo-controlled trial of low-dose aspirin or vitamin E. Their analysis focused on val158met, a common variant in the COMT gene: Individuals who are homozygous for the enzyme's high-activity valine form, the “val/vals,” have been shown to have lower levels of catecholamines compared to individuals who are homozygous for the enzyme's low-activity methionine form, the “met/mets,” The val/met heterozygotes are in between.

“When we examined women in the placebo arm of the trial, we found that the 23% of the women who were 'val/vals' were naturally protected against incident cardiovascular disease,” explains senior author Daniel I. Chasman, PhD. The investigation further revealed that when women with the val/val polymorphism were allocated to aspirin, this natural protection was eliminated. Among the 28% of women who were met/mets, the opposite was true, and these women had fewer cardiovascular events when assigned to aspirin compared to placebo. Read the study abstract.

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