Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: Apopulation 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

Research output: Contribution to journalArticle

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 followup 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 - 2016

Keywords

  • Blood pressure
  • Hypertension
  • Mean arterial pressure
  • Pulse pressure
  • Reactive oxygen species
  • Uric acid
  • Xanthine dehydrogenase
  • Xanthine oxidase
  • Xanthine oxidoreductase

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • 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: Apopulation study. Journal of Hypertension, 34(11), 2147 - 2154. https://doi.org/10.1097/HJH.0000000000001077