Effect of hydrochlorothiazide on serum uric acid concentration: a genome-wide association study

Pharmacogenomics. 2018 Apr;19(6):517-527. doi: 10.2217/pgs-2017-0184. Epub 2018 Mar 27.

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.

Trial registration: ClinicalTrials.gov NCT03276598 NCT00338260.

Keywords: hydrochlorothiazide; pharmacogenomics; uric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antihypertensive Agents
  • BRINP3 protein, human
  • DNA-Binding Proteins
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C
  • Hydrochlorothiazide
  • Uric Acid
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases

Associated data

  • ClinicalTrials.gov/NCT03276598
  • ClinicalTrials.gov/NCT00338260