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, 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 ; Vol. 34, No. 11. pp. 2147-2154.
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title = "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 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.",
author = "Scheepers, {Lieke E J M} and Fang-Fei Wei and Katarzyna Stolarz-Skrzypek and Sofia Malyutina and Val{\'e}rie Tikhonoff and Lutgarde Thijs and Erika Salvi and Cristina Barlassina and Jan Filipovsk{\'y} and Edoardo Casiglia and Yuri Nikitin and Kalina Kawecka-Jaszcz and Paolo Manunta and Daniele Cusi and Annelies Boonen and Staessen, {Jan A} and Arts, {Ilja C W}",
year = "2016",
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doi = "10.1097/HJH.0000000000001077",
language = "English",
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Scheepers, LEJM, 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, JA & Arts, ICW 2016, 'Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study', Journal of Hypertension, vol. 34, no. 11, pp. 2147-2154. 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, Vol. 34, No. 11, 11.2016, p. 2147-2154.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Xanthine oxidase gene variants and their association with blood pressure and incident hypertension

T2 - a population study

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

PY - 2016/11

Y1 - 2016/11

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.

AB - 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.

U2 - 10.1097/HJH.0000000000001077

DO - 10.1097/HJH.0000000000001077

M3 - Article

C2 - 27607461

VL - 34

SP - 2147

EP - 2154

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 11

ER -