Key result
GWAS links specific genetic variants to BP and glucose responses to chlorthalidone in African Americans.
Why the study?
Interpersonal differences in BP response to antihypertensive treatment suggest a genetic component, prompting study into variants associated with chlorthalidone efficacy and fasting glucose changes in African Americans.
Do specific genetic variants affect blood pressure and fasting glucose responses to chlorthalidone in African Americans with hypertension?
RCT (n=4,297)
Yes
Do specific genetic variants affect blood pressure and fasting glucose responses to chlorthalidone in African Americans with hypertension?
Specific genetic variants may influence blood pressure reduction and adverse fasting glucose changes in African Americans treated with chlorthalidone, highlighting potential pharmacogenomic pathways for personalized hypertension management.
Variants may guide future pharmacogenomic research on chlorthalidone; leaves open clinical utility pending validation.
Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population.
No takes yet. Share an insight, caveat, or question.
Armstrong et al. (2022) conducted an RCT in Hypertension (n=4,297). Chlorthalidone was evaluated on Change of systolic and diastolic BP over six months and fasting glucose levels over 24 months. Genome-wide association analyses of African Americans treated with chlorthalidone identified 8 variants associated with blood pressure response and 9 variants associated with fasting glucose response.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: