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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
JournalJournal of Hypertension
DOIs
Publication statusAccepted/In press - Sep 6 2016

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Xanthine Dehydrogenase
Xanthine Oxidase
Blood Pressure
Hypertension
Uric Acid
Alleles
Population
Genes
Arterial Pressure
Confidence Intervals
Single Nucleotide Polymorphism
Reactive Oxygen Species
Odds Ratio
Incidence
Enzymes
Serum

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Medicine(all)
  • Cardiology and Cardiovascular Medicine

Cite this

Scheepers, L. E. J. M., Wei, F. F., Stolarz-Skrzypek, K., Malyutina, S., Tikhonoff, V., Thijs, L., ... Arts, I. C. W. (Accepted/In press). Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. Journal of Hypertension. https://doi.org/10.1097/HJH.0000000000001077

Xanthine oxidase gene variants and their association with blood pressure and incident hypertension : a population study. / Scheepers, Lieke E J M; Wei, Fang Fei; Stolarz-Skrzypek, Katarzyna; Malyutina, Sofia; Tikhonoff, Valérie; Thijs, Lutgarde; Salvi, Erika; Barlassina, Cristina; Filipovský, Jan; Casiglia, Edoardo; Nikitin, Yuri; Kawecka-Jaszcz, Kalina; Manunta, Paolo; Cusi, Daniele; Boonen, Annelies; Staessen, Jan A.; Arts, Ilja C W.

In: Journal of Hypertension, 06.09.2016.

Research output: Contribution to journalArticle

Scheepers, LEJM, Wei, FF, 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, JA & Arts, ICW 2016, 'Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study', Journal of Hypertension. https://doi.org/10.1097/HJH.0000000000001077
Scheepers, Lieke E J M ; Wei, Fang Fei ; Stolarz-Skrzypek, Katarzyna ; Malyutina, Sofia ; Tikhonoff, Valérie ; Thijs, Lutgarde ; Salvi, Erika ; Barlassina, Cristina ; Filipovský, Jan ; Casiglia, Edoardo ; Nikitin, Yuri ; Kawecka-Jaszcz, Kalina ; Manunta, Paolo ; Cusi, Daniele ; Boonen, Annelies ; Staessen, Jan A. ; Arts, Ilja C W. / Xanthine oxidase gene variants and their association with blood pressure and incident hypertension : a population study. In: Journal of Hypertension. 2016.
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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.",
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AU - Scheepers, Lieke E J M

AU - Wei, Fang Fei

AU - Stolarz-Skrzypek, Katarzyna

AU - Malyutina, Sofia

AU - Tikhonoff, Valérie

AU - Thijs, Lutgarde

AU - Salvi, Erika

AU - Barlassina, Cristina

AU - Filipovský, Jan

AU - Casiglia, Edoardo

AU - Nikitin, Yuri

AU - Kawecka-Jaszcz, Kalina

AU - Manunta, Paolo

AU - Cusi, Daniele

AU - Boonen, Annelies

AU - Staessen, Jan A.

AU - Arts, Ilja C W

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N2 - 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.

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