Hydrochlorothiazide-induced hyperuricaemia in the pharmacogenomic evaluation of antihypertensive responses study

Journal of Internal Medicine
A G VandellJulie A Johnson

Abstract

Elevations in uric acid (UA) and the associated hyperuricaemia are commonly observed secondary to treatment with thiazide diuretics. We sought to identify novel single nucleotide polymorphisms (SNPs) associated with hydrochlorothiazide (HCTZ)-induced elevations in UA and hyperuricaemia. A genome-wide association study of HCTZ-induced changes in UA was performed in Caucasian and African American participants from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study who were treated with HCTZ monotherapy. Suggestive SNPs were replicated in Caucasians and African Americans from the PEAR study who were treated with HCTZ add-on therapy. Replicated regions were followed up through expression and pathway analysis. Five unique gene regions were identified in African Americans (LUC7L2, ANKRD17/COX18, FTO, PADI4 and PARD3B), and one region was identified in Caucasians (GRIN3A). Increases in UA of up to 1.8 mg dL(-1) were observed following HCTZ therapy in individuals homozygous for risk alleles, with heterozygotes displaying an intermediate phenotype. Several risk alleles were also associated with an increased risk of HCTZ-induced clinical hyperuricaemia. A composite risk score, constructed in African Americans using...Continue Reading

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Jan 20, 2016·CPT: Pharmacometrics & Systems Pharmacology·D M RotroffR Kaddurah-Daouk
Jul 1, 2016·The Journal of Clinical Hypertension·Stephanie R MoulinJosé G Mill
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Related Concepts

Antihypertensive Agents
African American
Diuretic Effect
Sectrazide
Hypertensive Disease
Pharmacogenomics
Single Nucleotide Polymorphism
Hyperuricemia
European Continental Ancestry Group
Genome-Wide Association Study

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