Genome Wide Association Study Identifies the HMGCS2 Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients

Background Thiazide and thiazide‐like diuretics are first‐line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to i...

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Bibliographic Details
Published in:Journal of the American Heart Association 2018-03, Vol.7 (6), p.n/a
Main Authors: Singh, Sonal, McDonough, Caitrin W., Gong, Yan, Alghamdi, Wael A., Arwood, Meghan J., Bargal, Salma A., Dumeny, Leanne, Li, Wen‐Yi, Mehanna, Mai, Stockard, Bradley, Yang, Guang, Oliveira, Felipe A., Fredette, Natalie C., Shahin, Mohamed H., Bailey, Kent R., Beitelshees, Amber L., Boerwinkle, Eric, Chapman, Arlene B., Gums, John G., Turner, Stephen T., Cooper‐DeHoff, Rhonda M., Johnson, Julie A.
Format: Article
Language:English
Subjects:
Adult
African Americans - genetics
Antihypertensive Agents - adverse effects
Biomarkers - blood
Blood Glucose - drug effects
Blood Glucose - metabolism
Blood Pressure - drug effects
chlorthalidone
Chlorthalidone - adverse effects
diabetes mellitus
Essential Hypertension - drug therapy
Essential Hypertension - ethnology
Essential Hypertension - physiopathology
European Continental Ancestry Group - genetics
Female
Genome-Wide Association Study
glucose
Humans
hydrochlorothiazide
Hydroxymethylglutaryl-CoA Synthase - genetics
hyperglycemia
Hyperglycemia - blood
Hyperglycemia - chemically induced
Hyperglycemia - ethnology
Hyperglycemia - genetics
Male
Middle Aged
Original Research
Pharmacogenomic Variants
pharmacogenomics
Phenotype
Polymorphism, Single Nucleotide
Randomized Controlled Trials as Topic
Risk Factors
Sodium Chloride Symporter Inhibitors - adverse effects
United States - epidemiology
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Summary:Background Thiazide and thiazide‐like diuretics are first‐line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide‐like diuretic/chlorthalidone‐induced glucose change. Methods and Results Genome‐wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR‐2 (Pharmacogenomic Evaluation of Antihypertensive Responses‐2). Single‐nucleotide polymorphisms with P
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.117.007339