Genetic Analysis of African-Americans With High Blood Pressure

Overview

The purpose of this study is to learn if kinase, a protein found in the heart, contributes to thickening of the heart muscle in people with high blood pressure. A protein called myosin causes the heart to contract and relax. It is thought that kinase changes myosin to make it work better at different heart rates. This study will try to determine if, in some people with high blood pressure, the different forms of this protein cause changes in the heart. If the protein affects the size of the heart, it might be possible to use it to improve heart function after an injury, such as a heart attack. African-Americans with high blood pressure will be eligible for this study. Current data show that of almost 900 multi-ethnic individuals, the particular form of kinase under study in this project is found exclusively in the African-American population. Study participants will have two tubes of blood drawn for DNA testing to determine what form of kinase is present. An electrocardiogram will also be done if a recent one is not available. Some people may also have an echocardiogram, an ultrasound test to image the heart.

Genetic and in vitro mechanical studies in our laboratory have suggested that the perturbations in the phosphorylation of the cardiac myosin regulatory light chain (RLC) can modulate cardiac function and produce a compensatory hypertrophic response. We have cloned a novel human cardiac kinase (MLCK) that targets the cardiac RLC and identified a common allele unique to the African-American population. The purpose of this protocol is to evaluate a large group of African-American individuals with hypertension and/or cardiac disease, a portion of who will possess this allele. It is well documented that hypertensive African-Americans have an increased prevalence of left ventricular hypertrophy (LVH). We expect that, in this population of hypertensive individuals, we will find an increased left ventricular mass in individuals who are heterozygous or homozygous for this kinase allele. In this study, patients with the allele can be matched to others in the cohort without the allele and evaluated by echocardiography and cardiac MRI to evaluate cardiac function and chamber size. In addition, metabolic stress testing will be performed to assess the implications of this allele on clinical performance. Another group of 75 Afro-Americans with dilated cardiomyopathy will be referred from local heart failure clinics and evaluated in a similar fashion. Allele prevalence and associated cardiac findings will also be compared with hypertensive patients matched for age and gender. In a parallel experiment, mice over-expressing this kinase, are being generated and will provide us with tissue samples with which to pursue the biophysical basis of the mechanical changes in muscle function.