Genetic Analysis of African-Americans With High Blood Pressure

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.

- INCLUSION CRITERIA:

Inclusion Criteria (Main Cohort):

Afro-American patients with a history of hypertension

Age greater than or equal to 21 years old

Presence of the kinase allele (homo or heterozygous)

Ability to give informed consent.

Inclusion Criteria (Myopathy Cohort):

All of the above as well as:

Left ventricular ejection fraction of less than 35% by any imaging technique.

EXCLUSION CRITERIA

For subjects with Kinase Allele:

There will be no exclusion criteria. Patients will be evaluated even if they are only able
to participate in part of the study.

For Subjects without the kinase allele and Myopathy Cohort:

History of myocardial infarction

History of significant valve disease

History of primary hyperthropic or infiltrative cardiomyopathy

History of rheumatic heart disease

Chronic atrial arrhythmia, bundle branch block intraventricular conduction defect or
definite myocardial infarction on EKG

Inability to perform a metabolic stress test

Inability to perform a cMRI

Poor echocardiographic windows precluding accurate analysis