INVESTIGATION OF THE GENETIC AND ENVIRONMENTAL EFFECTS ON HYPERTENSION (HIGH BLOOD PRESSURE) IN AFRICAN AMERICANS

Open Access
Author:
Yao, Xiaopan
Graduate Program:
Genetics
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
March 01, 2007
Committee Members:
  • George Patrick Vogler, Committee Chair
  • David John Vandenbergh, Committee Member
  • Keith Whitfield, Committee Member
  • Karen Boomer, Committee Member
  • Runze Li, Committee Member
Keywords:
  • hypertension
Abstract:
According to the National Center for Health Statistics, African Americans have among the highest rates of hypertension of any race or ethnic type in the world. Thirtyfive percent of African Americans have hypertension, which accounts for 20% of the African American deaths in the United States. This project addresses the question of genetic predisposition and environmental effects on hypertension in a population of African Americans through biological and statistical approaches. The primary objectives of this project are to (1) identify relevant gene(s) associated with hypertension in the population of African Americans by evaluating several candidate genes; (2) to investigate the genetic and environmental effects on hypertension in African Americans. Three Single Nucleotide Polymorphisms(SNPs) were chosen from three primary genes of the renin-angiotensin system. These three SNPs were M235T in the Angiotensinogen (AGT) gene, A-240T in the Angiotensin I Converting Enzyme (ACE) gene, and A44221G in the Angiotensinogen II receptor, subtype 1 (AGTR1) gene. A total of 706 African Americans, including 101 monozygotic twin pairs (MZ twins), 182 dizygotic twin pairs (DZ twins), 31 sibling pairs, and 78 singletons, were interviewed and genotyped at the three genetic loci. There were three steps in this project. Association tests and logistic regression analyses were performed to investigate the association between hypertension status and the three SNPs separately to find the gene(s) associated with high blood pressure in the population of African Americans. Next two general linear mixed models were built to explain the effect of particular relevant gene(s) and the effect of other determining factors on blood pressure in African Americans. Finally structural equation modeling (SEM) was used to estimate the genetic and environmental effects on blood pressure in African Americans. The measured genotype of the relevant gene(s) that had been detected by association tests were added into the traditional SEM with the aim to estimate the effect of particular genetic loci separately from the effect of unmeasured genetic factors and to assess the importance of particular gene(s) relative to the influence of genetic effects in sum.