Genetic Analysis of African-American Hypertensives

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.