Background: Uric acid has been associated with blood pressure and hypertension. During the final stage of purine metabolism xanthine oxidoreductase (XOR) produces uric acid, while at the same time reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension.
Objectives: The aim of the present study is to investigate the association of variants in the XOR gene with blood pressure and the development of hypertension.
Methods: Analyses were conducted in the prospective Flemish FLEMENGHO and European EPOGH study. Among 2769 participants (48.3% men; mean age 40.7 years) we genotyped 25 XOR SNPs and measured blood pressure 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 analysed using multivariable mixed models and cox-regression, respectively.
Results: Compared with major allele homozygotes, pulse pressure increased approximately 2 mm Hg more in minor allele carriers of rs11904439 (P=value 0.01), whereas mean arterial pressure and diastolic blood pressure increased approximately 1 mm Hg 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. major allele homozygotes was 1.31 (95% confidence interval [CI] 1.03–1.68) for rs11904439 and 1.69 (95% CI 1.11–2.57) for rs148756340. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in systolic blood pressure from baseline to follow-up and the serum levels of uric acid at baseline (n=1949) were not associated with XOR.
Conclusions: In conclusion, pending confirmation in appropriately powered cohort studies, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in pulse pressure, mean arterial pressure and in the risk of hypertension.
Acknowledgement: The authors gratefully acknowledge the clerical assistance of Mrs Renilde Wolfs.