Title | Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Del-Aguila, JL, Cooper-Dehoff, RM, Chapman, AB, Gums, JG, Beitelshees, AL, Bailey, K, Turner, ST, Johnson, JA, Boerwinkle, E |
Journal | Pharmacogenomics J |
Volume | 15 |
Issue | 2 |
Pagination | 153-7 |
Date Published | 2015 Apr |
ISSN | 1473-1150 |
Keywords | Antihypertensive Agents, Bayes Theorem, Black or African American, Carrier Proteins, Cation Transport Proteins, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 8, Female, Genome-Wide Association Study, Heme, Heme-Binding Proteins, Hemeproteins, Humans, Hydrochlorothiazide, Hypertension, Hypokalemia, Male, Middle Aged, Mitochondrial Proteins, Polymorphism, Single Nucleotide, Potassium, White People |
Abstract | Hypokalemia is a recognized adverse effect of thiazide diuretic treatment. This phenomenon, which may impair insulin secretion, has been suggested to be a reason for the adverse effects on glucose metabolism associated with thiazide diuretic treatment of hypertension. However, the mechanisms underlying thiazide diuretic-induced hypokalemia are not well understood. In an effort to identify genes or genomic regions associated with potassium response to hydrochlorothiazide, without a priori knowledge of biologic effects, we performed a genome-wide association study and a multiethnic meta-analysis in 718 European- and African-American hypertensive participants from two different pharmacogenetic studies. Single-nucleotide polymorphisms rs10845697 (Bayes factor=5.560) on chromosome 12, near to the HEME binding protein 1 gene, and rs11135740 (Bayes factor=5.258) on chromosome 8, near to the Mitoferrin-1 gene, reached genome-wide association study significance (Bayes factor >5). These results, if replicated, suggest a novel mechanism involving effects of genes in the HEME pathway influencing hydrochlorothiazide-induced renal potassium loss. |
DOI | 10.1038/tpj.2014.46 |
Alternate Journal | Pharmacogenomics J |
PubMed ID | 25201287 |
PubMed Central ID | PMC4362777 |
Grant List | M01 RR00039 / RR / NCRR NIH HHS / United States HL53335 / HL / NHLBI NIH HHS / United States U01 GM074492 / GM / NIGMS NIH HHS / United States M01 RR000039 / RR / NCRR NIH HHS / United States HL74735 / HL / NHLBI NIH HHS / United States UL1 TR001427 / TR / NCATS NIH HHS / United States UL1 TR000454 / TR / NCATS NIH HHS / United States R01 HL074735 / HL / NHLBI NIH HHS / United States UL1 RR024150 / RR / NCRR NIH HHS / United States M01 RR00082 / RR / NCRR NIH HHS / United States UL1 RR025008 / RR / NCRR NIH HHS / United States M01 RR000082 / RR / NCRR NIH HHS / United States UL1 RR029890 / RR / NCRR NIH HHS / United States |
Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide.
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