Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide.
Pharmacogenomics J
; 15(2): 153-7, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25201287
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Potássio
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Proteínas de Transporte
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Polimorfismo de Nucleotídeo Único
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Heme
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Hemeproteínas
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Hidroclorotiazida
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Anti-Hipertensivos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article