OA01.04 LB
Purpose: Despite the lack of conclusive evidence of efficacy from well-designed clinical trials, the use of vitamins remains widespread. With recent reports of possible harm, the debate has shifted from benefits relative to placebo, to concerns about safety. Few studies have investigated the effect of genetic variation on treatment responses to vitamin E. Genetic variation is considered an important factor in heritability of CVD and treatment response. Catecholamines like epinephrine play a key role in cardiovascular function and are metabolized by catechol-O-methyltransferase (COMT). The effect of genetic variation in COMT on CVD outcomes in women treated with vitamin E is not known.
Methods: The Women's Health Study (WHS) is a large prospective placebo-controlled trial of incident CVD prevention with random allocation to aspirin and vitamin E and 10 years follow-up. The Women's Genome Health Study (WGHS), a large subset of the WHS for genetic analysis provided a unique dataset to examine the effects of the COMT rs4680 polymorphism.
Results: The rs4680 high-activity val allele was protective for incident CVD among women in the placebo arm (HR[95%CI]=0.66[0.51–0.84], P=0.0007) such that val homozygotes had a 56% lower rate of major CVD relative to low-activity met homozygotes. The rs4680 protective association was abolished by randomized allocation to vitamin E such that val homozygotes experienced higher rates of major CVD with vitamin E compared to placebo (HR[95%CI]=1.50[0.83–2.70], P=0.180), while met homozygotes experienced lower rates (HR[95%CI]=0.53[0.34–0.84], P=0.023) thus revealing a significant interaction between COMT and vitamin E (P=0.004).
Conclusion: Common COMT polymorphism association with CVD risk and differential effects of vitamin E treatment suggests novel aspects of CVD pathophysiology. In an era where the use of vitamins is under debate, this study highlights the importance of considering genetic composition in evaluating clinical efficacy of vitamins and using pharmacogenomics to guide the development of smarter, individualized strategies for treatment and prevention.
Contact: Kathryn Hall, kthall@bidmc.harvard.edu
