Genetic risk of hyperuricemia in hypertensive patients associated with antihypertensive drug therapy: A longitudinal study

Clin Genet. 2022 Apr;101(4):411-420. doi: 10.1111/cge.14110. Epub 2022 Jan 24.

Abstract

Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA-associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA-related variants at 29 genes in 1840 patients with hypertension from a community-based longitudinal cohort during a median 2.25-year follow-up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new-onset hyperuricemia). Compared with the wild-type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, β-blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow-up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.

Keywords: antihypertensive drug therapy; genetic risk; hyperuricemia; serum uric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / adverse effects
  • Diuretics / adverse effects
  • Glucose Transport Proteins, Facilitative / genetics
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / genetics
  • Hyperuricemia* / complications
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / genetics
  • Longitudinal Studies
  • Risk Factors
  • Uric Acid / therapeutic use

Substances

  • Antihypertensive Agents
  • Diuretics
  • Glucose Transport Proteins, Facilitative
  • SLC2A9 protein, human
  • Uric Acid