Genaissance Study Sheds Light on Mechanism of Heart Disease Risk

Genaissance Pharmaceuticals has said a study it conducted on 674 subjects suggests that women with a genetic predisposition to protective levels of C-reactive protein (CRP) lose that benefit when taking hormone replacement therapy (HRT).

The results of this study were published in the December 2004 issue of Atherosclerosis.

The study, a pioneering look at how genetic markers might be responsible for differential response to statin drugs for lowering cholesterol, found that women who were on HRT lost the protective benefits of certain genetic variants that would normally predispose them to lower levels of CRP, an established marker for fatal coronary disease.

The results of this study are the first published result from Genaissance's STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study, the largest prospective pharmacogenetic study ever undertaken to find genetic markers responsible for differential response to statin drugs for lowering cholesterol, according to the company. The eight-month study of 315 men and 359 women also was designed to find genetic markers responsible for pretreatment levels of important biomarkers such as low-density lipoprotein, high-density lipoprotein and CRP.

The results give lifestyle guidance to women who would like to preserve the protective benefits conferred by favorable genetic variations, and may ultimately lead to new or modified drugs. The study showed that men and women with common variants in the apolipoprotein E gene on average have naturally lower levels of CRP. In the case of women, however, the study indicates that this beneficial effect may be largely neutralized by HRT, allowing CRP levels to potentially increase to dangerous levels.