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• W2078491345 abstract "Abstract Objective 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 ( SNP s) associated with hydrochlorothiazide ( HCTZ )‐induced elevations in UA and hyperuricaemia. Methods A genome‐wide association study of HCTZ ‐induced changes in UA was performed in C aucasian and A frican A merican participants from the pharmacogenomic evaluation of antihypertensive responses ( PEAR ) study who were treated with HCTZ monotherapy. Suggestive SNP s 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. Results Five unique gene regions were identified in A frican A mericans ( LUC7L2 , ANKRD17 / COX18 , FTO , PADI4 and PARD3B ), and one region was identified in C aucasians ( 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 the ‘top’ SNP from each gene region, was strongly associated with HCTZ ‐induced UA elevations ( P = 1.79 × 10 −7 ) and explained 11% of the variability in UA response. Expression studies in RNA from whole blood revealed significant differences in expression of FTO by rs4784333 genotype. Pathway analysis showed putative connections between many of the genes identified through common micro RNA s. Conclusion Several novel gene regions were associated with HCTZ ‐induced UA elevations in African Americans ( LUC 7L2 , COX 18 / ANKRD 17 , FTO , PADI 4 and PARD 3B ), and one region was associated with these elevations in C aucasians ( GRIN 3A )." @default.
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• W2078491345 date "2014-02-28" @default.
• W2078491345 modified "2023-10-18" @default.
• W2078491345 title "Hydrochlorothiazide‐induced hyperuricaemia in the pharmacogenomic evaluation of antihypertensive responses study" @default.
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• W2078491345 doi "https://doi.org/10.1111/joim.12215" @default.
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