Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study

J Hypertens. 2016 Nov;34(11):2147-54. doi: 10.1097/HJH.0000000000001077.

Abstract

Objective: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension.

Methods: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed.

Results: Compared with nonminor allele carriers, pulse pressure increased approximately 2 mmHg more in minor allele carriers of rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11-2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to follow-up and the serum levels of uric acid at baseline (n = 1949) were not associated with XOR.

Conclusion: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Arterial Pressure / genetics
  • Belgium / epidemiology
  • Blood Pressure / genetics*
  • Czech Republic / epidemiology
  • Diastole / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Heterozygote
  • Humans
  • Hypertension / epidemiology*
  • Hypertension / genetics*
  • Incidence
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Poland / epidemiology
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • Prospective Studies
  • Russia / epidemiology
  • Uric Acid / blood*
  • Xanthine Oxidase / genetics*
  • Xanthine Oxidase / metabolism
  • Young Adult

Substances

  • Uric Acid
  • Xanthine Oxidase