All ETDs from UAB

Advisory Committee Chair

Ryan M Irvin

Advisory Committee Members

Stella Aslibekyan

Nita A Limdi

Sanjiv J Shah

Hemant K Tiwari

Degui Zhi

Document Type

Dissertation

Date of Award

2017

Degree Name by School

Doctor of Philosophy (PhD) School of Public Health

Abstract

The purpose of this dissertation is to evaluate the association of antihypertensive treatment as well genomic variants with left ventricular (LV) hypertrophy (LVH) -related traits among African Americans (AAs) in five cross-sectional epidemiology cohorts from the United States. AAs especially those with hypertension, are overburdened by left ventricular (LV) hypertrophy (LVH) compared to other ethnic groups. LVH is associated with increased risk for cardiovascular morbidity and mortality. Antihypertensive treatments have been found to improve LVH and related echocardiographic measures (i.e. LV traits) among hypertensive patients. However, the effect of antihypertensive treatments on LVH and related traits in AAs has not been well studied. Furthermore, high heritability of LV traits (e.g. LV mass heritability in AAs is 34%) and variability of the response to antihypertensive treatments suggests genetic factors may be involved. The first aim evaluated the association of rare variants with LV traits among AAs using exome chip data from the Hypertension Genetic Epidemiology Network study (HyperGEN) and Genetic Epidemiology Network of Atherosclerosis study (GENOA) studies. The second aim evaluated the main effect of the three most common antihypertensive treatments for AAs as well as SNP-by-drug interaction effects on LV traits in five cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Antihypertensive treatments considered included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs). The third aim evaluated the interaction between CpGs and TDs, ACE-Is and dCCBs on LV traits using data from AAs from the HyperGEN and GENOA studies. We found that TDs may be better for prevention of LVH in comparison to dCCBs in AAs. It also suggests that common variants could modify the association between antihypertensive treatment and LV traits in AAs. In addition, rare protein coding variants could be important contributors to LV structures and LV functions in AAs. A strength of this body of work is that these are some of the first investigations of these exposures and traits among AAs. Future sequencing studies that capture more variants in larger populations of AAs treated for hypertension are needed to expand these findings here.

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