Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study
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 2mmHg more in minor allele carriers of rs11904439 (P=0.01), whereas mean arterial pressure and DBP increased approximately 1mmHg 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.