Mitochondrial Haplogroup Association with Fasting Glucose Response in African Americans Treated with a Thiazide Diuretic

Abstract

Hypertensive African Americans have ~50% response rate to thiazide diuretic treatment. This contributes to a high prevalence of uncontrolled high blood pressure. Here, we examine the role the mitochondrial genome has on thiazide diuretic treatment response in hypertensive African Americans enrolled in a clinical trial. Participants from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT, n= 4279) were genotyped using the Illumina Infinium Multi-Ethnic Beadchip. Haplotype groups were called using HaploGrep. We used linear regression analysis to examine the association between mitochondrial haplogroups (L, M, and N) and change in blood pressure and change in fasting glucose over 6 months and two years, respectively. The analysis revealed a null association between mitochondrial haplogroups M and N vs. L for each of the outcomes. In subgroup analysis, the L subclades L1, L2, and L3/L4 (vs. L0) were each inversely associated with fasting glucose response (p < 0.05). This discovery analysis suggests the mitochondrial genome has a small effect on fasting glucose but not blood pressure response to thiazide diuretic treatment in African Americans.