All ETDs from UAB

Advisory Committee Chair

Ryan Irvin

Advisory Committee Members

Hemant K Tiwari

Stella Aslibekyan

Zechen Chong

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Research shows African Americans are more likely to suffer from a chronic disease compared to other American populations. Due to the fact that African Americans are extremely underrepresented within human health research, the potential biological causes of the racial/ethnic differences are not well understood. Some of these health differences may be due to genomic variations within either the mitochondrial genome, nuclear genome, or both. To aid the revolution of inclusive human health research, we examined genomic factors related to cardiometabolic diseases in African Americans.African Americans have the highest prevalence of hypertension compared to all other American populations. With the majority of African Americans treated with a diuretic to combat the effects of hypertension. However, African Americans continue to have the lowest prevalence of controlled hypertension compared to all other American populations. The racial difference in the response to antihypertensive treatment is not well understood. Recently, researchers are examining the mitochondrial genome because of its links to metabolism and drug response. Several studies have observed mitochondrial genomic variations significantly associated to several diseases like, cardiovascular disease and type-2-diabetes. Thus, we examined how mitochondrial genetic factors affect African American’s varied blood pressure and metabolic response to thiazide diuretics. Results revealed mitochondrial genome may play a small role in varied glucose but not blood pressure response to thiazide diuretic. Metabolic Syndrome is a cluster of deleterious traits that can lead to cardiovascular disease and increased mortality. Studies have observed epigenomic affects like DNA methylation, significantly linked to metabolic syndrome. Since, it is known that methylation has been significantly linked to several diseases, it is no surprise that several studies have discovered specific cytosine-guanine methylation sites associated with metabolic syndrome. Hence, we created a metabolic syndrome risk score based on cytosine-phosphate-guanine (CpG) methylation within an African American population. We were able to use a European population to validate the risk score. Our methylation risk score was able to significantly predict the risk of metabolic syndrome, revealing the potential use for a generalizable metabolic syndrome predicting risk score.

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