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

Lieke E J M Scheepers, Fang-Fei Wei, Katarzyna Stolarz-Skrzypek, Sofia Malyutina, Valérie Tikhonoff, Lutgarde Thijs, Erika Salvi, Cristina Barlassina, Jan Filipovský, Edoardo Casiglia, Yuri Nikitin, Kalina Kawecka-Jaszcz, Paolo Manunta, Daniele Cusi, Annelies Boonen, Jan A Staessen, Ilja C W Arts

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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.

Original languageEnglish
Pages (from-to)2147-2154
Number of pages8
JournalJournal of Hypertension
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2016

Cite this

Scheepers, L. E. J. M., Wei, F-F., Stolarz-Skrzypek, K., Malyutina, S., Tikhonoff, V., Thijs, L., Salvi, E., Barlassina, C., Filipovský, J., Casiglia, E., Nikitin, Y., Kawecka-Jaszcz, K., Manunta, P., Cusi, D., Boonen, A., Staessen, J. A., & Arts, I. C. W. (2016). Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. Journal of Hypertension, 34(11), 2147-2154. https://doi.org/10.1097/HJH.0000000000001077