Currently available data indicate that there are significant health care disparities among ethnic and racial minority groups. In addition, there are important differences in response to conventional pharmacologic therapies among these groups. Although there are many potential explanations for this observation, including environmental and socioeconomic factors, one potential explanation is that the genetic predisposition to disease and to differences in drug response differs among racial and ethnic groups. The current study is a supplement to a large multi-investigator grant (Pharmacogenetics of Membrane Transporters) to determine the pharmacogenetics of a number of membrane transporters which are important determinants of pharmacokinetics and/or pharmacodynamics of drug substrates. The overall objective of the studies proposed in this supplement is to establish a local cohort of 500 healthy volunteers recruited from four racial/ethnic groups (Chinese, African American, Mexican American, and Caucasians). We will recruit a local cohort of ethnically diverse subjects who will undergo phenotype analysis and genetic testing of candidate genes thought to be involved in the transport of medications such as anti-hypertensive drugs. A special feature of this cohort is that the volunteers will be available to be called back to participate in future studies that relate genotype to pharmacokinetic properties of drugs that are substrates of membrane transporters. As part of the overall PMT project, these genetic variants will be further tested with in vitro functional assays to determine the biologic relevance of the identified genetic variants. Subjects will be stratified by their respective genotypes and then undergo pharmacologic testing with conventional therapies. These investigations will allow us to determine whether pharmacogenetic relationships exist and allow us to identify ethnic-specific genotypic differences in drug response. The overall aim of this proposal is to better understand the genetic factors that may contribute to the increased disparity from disease existing in ethnically diverse populations. This goal is consistent with goals established by the Healthy People initiative, which aims to reduce disparities in health among different population groups.