%0 Journal Article %J Pharmacogenomics J %D 2015 %T Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide. %A Del-Aguila, J L %A Cooper-Dehoff, R M %A Chapman, A B %A Gums, J G %A Beitelshees, A L %A Bailey, K %A Turner, S T %A Johnson, J A %A Eric Boerwinkle %K Antihypertensive Agents %K Bayes Theorem %K Black or African American %K Carrier Proteins %K Cation Transport Proteins %K Chromosomes, Human, Pair 12 %K Chromosomes, Human, Pair 8 %K Female %K Genome-Wide Association Study %K Heme %K Heme-Binding Proteins %K Hemeproteins %K Humans %K Hydrochlorothiazide %K Hypertension %K Hypokalemia %K Male %K Middle Aged %K Mitochondrial Proteins %K Polymorphism, Single Nucleotide %K Potassium %K White People %X

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.

%B Pharmacogenomics J %V 15 %P 153-7 %8 2015 Apr %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/25201287?dopt=Abstract %R 10.1038/tpj.2014.46