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Pharmacogenomics ; 19(6): 517-527, 2018 04.
Article in English | MEDLINE | ID: mdl-29580174

ABSTRACT

AIM: To recognize genetic associations of hydrochlorothiazide-induced change in serum uric acid (SUA) concentration. PATIENTS & METHODS: We conducted a genome-wide association study on hydrochlorothiazide-induced change in SUA in 214 Finnish men from the GENRES study. Replication analyses were performed in 465 Finns from the LIFE study. RESULTS: In GENRES, we identified 31 loci associated with hydrochlorothiazide-induced change in SUA at p < 5 × 10-5. rs1002976 near VEGFC associated with the change in GENRES and in LIFE. rs950569 near BRINP3 associated with the change in SUA in GENRES and LIFE. The analysis of previously reported SNPs and candidate genes provided some proof for PADI4 and ABCC4. CONCLUSION: We report genetic markers that may predict the increase in SUA concentration during thiazide treatment.


Subject(s)
Hydrochlorothiazide/adverse effects , Hypertension/genetics , Hyperuricemia/genetics , Uric Acid/blood , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , DNA-Binding Proteins/genetics , Female , Finland , Genome-Wide Association Study , Humans , Hydrochlorothiazide/administration & dosage , Hypertension/blood , Hypertension/complications , Hypertension/drug therapy , Hyperuricemia/blood , Hyperuricemia/complications , Hyperuricemia/pathology , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Protein-Arginine Deiminase Type 4 , Protein-Arginine Deiminases/genetics , Vascular Endothelial Growth Factor C/genetics
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