Beta-Blocker Pharmacogenetics in Ethnic Populations

It is well known that there are differences between African Americans and Caucasians with respect to the antihypertensive response to beta-blocker drugs. The largest studies on this topic suggest that about 40 percent of African Americans and 60 percent of Caucasians have a good antihypertensive response to beta-blockers. Little is known about the response of Hispanics to beta-blockers, compared to that of other ethnic populations. We propose to collect genetic samples from African Americans, Caucasians, and Hispanic hypertensive patients who are current participants in The INternational VErapamil/Trandolapril STudy (INVEST). We propose to collect genetic samples from at least 300 Caucasians, 300 Hispanics (mostly Puerto Ricans) and 150 African Americans, utilize existing INVEST clinical data, and test the following hypotheses. Hypothesis la: Variation in genes encoding the beta-1-adrenergic receptor (beta₁AR), Gs protein, and/or beta₂AR are important determinants of the antihypertensive effects of beta-blockers. Hypothesis lb: The apparent ethnic differences in beta-blocker response are a reflection of ethnic differences in allelic frequencies of the polymorphisms that are critical to drug response. This study is important because it will provide solid, prospective data on the association between beta-AR's and G protein polymorphisms on the response to beta-blocker medications. It will also provide comparative data on beta-blocker response and beta-blocker pharmacogenetics in three ethnic populations, including Hispanics, for whom there is essentially no existing data. More importantly, it should provide insight into the basis for ethnic differences in antihypertensive response to beta-blockers. This is important because documentation that the apparent ethnic differences in response are in fact genetically based differences will help to argue against basing drug therapy on a person's skin color/ethnic background, but rather highlight the role of using genetic information to determine drug therapy.