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Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication


Xanthine oxidoreductase (XOR), a rate-limiting and catalyzing enzyme of uric acid formation in purine metabolism, is involved in reactive oxygen species generation. Plasma XOR activity has been shown to be a novel metabolic biomarker related to obesity, liver dysfunction, hyperuricemia, dyslipidemia, and insulin resistance. However, the association between plasma XOR activity and hypertension has not been fully elucidated. We investigated the association of hypertension with plasma XOR activity in 271 nondiabetic subjects (male/female: 119/152) who had not taken any medications in the Tanno–Sobetsu Study, a population-based cohort. Males had higher plasma XOR activity than females. Plasma XOR activity was positively correlated with mean arterial pressure (r = 0.128, P = 0.036). When the subjects were divided by the presence and absence of hypertension into an HT group (male/female: 34/40) and a non-HT group (male/female: 85/112), plasma XOR activity in the HT group was significantly higher than that in the non-HT group (median: 39 vs. 28 pmol/h/mL, P = 0.028). There was no significant difference in uric acid levels between the two groups. Multivariable logistic regression analysis showed that plasma XOR activity (odds ratio: 1.091 [95% confidence interval: 1.023–1.177] per 10 pmol/h/mL, P = 0.007) was an independent determinant of the risk for hypertension after adjustment for age, sex, current smoking and alcohol consumption, estimated glomerular filtration rate, brain natriuretic peptide, and insulin resistance index. The interaction of sex with plasma XOR activity was not significant for the risk of hypertension. In conclusion, plasma XOR activity is independently associated with hypertension in nondiabetic individuals who are not taking any medications.

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MF was supported by a grant from the Japan Society for the Promotion of Science.

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Correspondence to Masato Furuhashi.

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Conflict of interest

TM, TN, and SA in Sanwa Kagaku Kenkyusho Co., Ltd. developed the plasma XOR activity assay and measured the activity. This does not alter our adherence to sharing data and materials. There are no competing nonfinancial interests for any authors.

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Furuhashi, M., Higashiura, Y., Koyama, M. et al. Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication. Hypertens Res 44, 1213–1220 (2021).

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  • Hypertension
  • Uric acid
  • Xanthine dehydrogenase
  • Xanthine oxidase

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