Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension

Hypertens Res. 2020 Mar;43(3):220-226. doi: 10.1038/s41440-019-0356-x. Epub 2019 Nov 20.


We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Keywords: Blood pressure; Genetic factors; Hypertension; Renal function; Thiazide-like diuretic; Uric acid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amlodipine / pharmacology
  • Amlodipine / therapeutic use
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Cross-Over Studies
  • Diuretics / pharmacology
  • Diuretics / therapeutic use*
  • Essential Hypertension / blood
  • Essential Hypertension / drug therapy
  • Essential Hypertension / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Indapamide / pharmacology
  • Indapamide / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Uric Acid / blood*
  • Valsartan / pharmacology
  • Valsartan / therapeutic use


  • Angiotensin Receptor Antagonists
  • Calcium Channel Blockers
  • Diuretics
  • Amlodipine
  • Uric Acid
  • Valsartan
  • Indapamide