Scheepers, LEJM and Wei, F-F and Stolarz-Skrzypek, K and Malyutina, S and Tikhonoff, V and Thijs, L and Salvi, E and Barlassina, C and Filipovsky, J and Casiglia, E and Nikitin, Y and Kawecka-Jaszcz, K and Manunta, P and Cusi, D and Boonen, A and Staessen, JA and Arts, ICW, Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study, Journal of Hypertension, 34, (11) pp. 2147-2154. ISSN 0263-6352 (2016) [Refereed Article]
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 ¼ 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P ¼ 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 ¼ 0.02) and 1.69 (95% confidence interval 1.11–2.57; P ¼ 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 ¼ 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.
|Item Type:||Refereed Article|
|Keywords:||hypertension, urate, uric acid, xanthine oxidase, genes, blood pressure|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Cardiology (incl. cardiovascular diseases)|
|Objective Group:||Clinical health|
|Objective Field:||Diagnosis of human diseases and conditions|
|UTAS Author:||Scheepers, LEJM (Dr Lieke Scheepers)|
|Web of Science® Times Cited:||21|
|Deposited By:||Menzies Institute for Medical Research|
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