Genetic Study of Arterial Compliance and Endothelial Function (pilot)

Morehouse School Of Medicine, Atlanta GA

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): The objective of this pilot study is to develop and implement standardized methods for investigating both genetic and environmental determinants of endothelial function and arterial compliance (elasticity) in African Americans. African Americans have stiffer arteries and a higher prevalence of hypertension compared to other ethnic groups in the US. Specific genetic makeup and environmental factors may work together to influence the susceptibility. The specific aims of this pilot study are: 1) to develop standardized methods for collecting and validating family data from African-American hypertensive and normotensive probands, their family members and first-degree relatives; 2) to assess the difference in allele and genotype frequency, endothelial function, vascular compliance and blood pressure within and between the two sets of families; 3) to compare the distribution of genetic, behavioral, physical, psychosocial, biochemical and other environmental risk factors in families with or without high family risk of hypertension; and 4) to estimate preliminarily genetic and environmental determinants to familial clustering of risk factors, endothelial dysfunction, arterial stiffness and hypertension. The study will use family-based case-control design. We propose to recruit 5 African- American families in which probands (40% females) and at least one of their parents have hypertension, and 5 African-American families with probands (40% females) and both parents to be free of hypertension. Married individuals aged 30-50, who have both parents alive and at least two children and two siblings, will be included as probands in this study. An interviewer-administered questionnaire will be utilized to obtain information on participants. demographic, behaviors, lifestyles, medical history, and family history of cardiovascular disease, socioeconomic status and other cardiovascular risk factors. Participants will have physical examinations, and measurements of arterial compliance and brachial endothelial function. Blood samples will be obtained to determine genotypes of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE), blood chemistry, hematology and lipid profiles, and to establish cell lines for future genetic studies of arterial disease. Statistical analyses will be conducted to estimate the main effects of genetic and environmental risks for arterial stiffness and their interactions among gene-gene and gene-environmental factors, such as smoking or physical inactivity, controlling for other cardiovascular risk factors. This study has the potential to provide insights into strategies for recruiting multi-generational families within the African-American community and the etiology and pathogenesis of arterial disease which will allow the development of effective strategies for early prevention of arterial disease, and its sequelae in an under-studied and under- served population.