# Genomic Background of Blood Pressure Response to Thiazide Diuretic in African Americans

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $652,109

## Abstract

Abstract
African Americans (AA) are overburdened with hypertension compared to other racial groups in the United
States. The disorder often takes on a more severe form including earlier onset, resistance to treatment, and
earlier end organ damage suggesting the need for personalized medicine strategies for prevention and
treatment in this group. Observational studies and clinical trials have shown that commonly used
antihypertensive agents exert variable blood pressure (BP) lowering effects in ethnic populations. For example,
compared to Caucasians, AAs exhibit significantly poorer BP lowering response to beta-blocker, angiotensin
converting enzyme inhibitors (ACEIs) or angiotensin receptor blocker (ARB's), and a much better response to
calcium channel blockers (CCBs) and diuretics when used as monotherapy. The eighth Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure suggests calcium
channel blockers and diuretics should be the first-line antihypertensive therapy for AAs. However, data show
there is more variation in response to antihypertensive treatment classes within race groups than between
them. Despite the clinical reliance on thiazide diuretics for AAs, no large scale pharmacogenetic discovery
effort has been undertaken. Furthermore, there are concerns regarding metabolic side effects for this drug
class, including abnormal glucose tolerance and hypokalemia. This is of particular importance to patients of
African ancestry, who have a higher risk of developing diabetes, and often need to start treatment at a younger
age. More than half of published pharmacogenetic studies do not include AAs, and, among those that do, the
average sample size is small (<200). In order to overcome the limitations of previous research and enable
genetic discovery of genes and variants which predict blood pressure response as well as metabolic response
to thiazide diuretic, we will leverage data and specimens from 4830 AAs randomized to chlorthalidone from the
Genetics of Hypertension Associated Treatment (GenHAT) study, an ancillary study of the Antihypertensive
and Lipid lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Genomic discovery will be enriched for
African Ancestry genetic variations, functional variation, as well as known pharmacodynamic and
pharmacokinetic variants. We have established an agreement with the International Consortium for
Antihypertensives Pharmacogenomics Studies (ICAPS) for validation of our findings. Genes associated with
thiazide diuretic response will be evaluated for association with cardiovascular disease outcomes in AAs from
GENHAT and the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS). In sum, the
project will shed light on the mechanisms of thiazide diuretic response; potentially identify new treatment
targets; and identify genetic markers which can optimize treatment in this high risk population.

## Key facts

- **NIH application ID:** 9962467
- **Project number:** 5R01HL123782-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Marguerite R Irvin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $652,109
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962467

## Citation

> US National Institutes of Health, RePORTER application 9962467, Genomic Background of Blood Pressure Response to Thiazide Diuretic in African Americans (5R01HL123782-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962467. Licensed CC0.

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