Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine.
Sanwa Kagaku Kenkyusho Co., Ltd.
Circ J. 2018 Jun 25;82(7):1892-1899. doi: 10.1253/circj.CJ-18-0082. Epub 2018 Apr 10.
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR promotes oxidative stress-related tissue injury. We investigated the associations between metabolic parameters and plasma XOR activity measured by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry to detect [C,N]-uric acid using [C,N]-xanthine as a substrate.
A total of 627 Japanese subjects (M/F, 292/335) from the Tanno-Sobetsu Study, a population-based cohort, were recruited. Plasma XOR activity was significantly higher in males than in females, and habitual smoking was associated with elevation of activity. Plasma XOR activity was positively correlated with body mass index (BMI; r=0.323, P<0.001), waist circumference, blood pressure, and levels of liver enzymes including alanine transaminase (r=0.694, P<0.001), uric acid (r=0.249, P<0.001), triglycerides (r=0.312, P<0.001), hemoglobin A1c, fasting glucose, insulin and HOMA-R (r=0.238, P<0.001) as a marker of insulin resistance and was negatively correlated with high-density lipoprotein cholesterol level. On stepwise and multivariate regression analyses, BMI, smoking and levels of alanine transaminase, uric acid, triglycerides and HOMA-R were independent predictors of plasma XOR activity after adjustment for age and gender.
Plasma XOR activity is a novel biomarker of metabolic disorders in a general population.
黄嘌呤氧化还原酶（XOR）是一种酶，可催化次黄嘌呤和黄嘌呤形成尿酸，导致超氧化物和活性氧物质增加。XOR 的激活会促进与氧化应激相关的组织损伤。我们使用一种灵敏且准确的测定法，通过结合使用液相色谱和三重四极杆质谱法，使用 [C，N]-黄嘌呤作为底物来检测 [C，N]-尿酸，来测量代谢参数与血浆 XOR 活性之间的关联。
总共招募了来自基于人群的 Tanno-Sobetsu 研究的 627 名日本受试者（男/女，292/335）。男性的血浆 XOR 活性明显高于女性，习惯性吸烟与活性升高有关。血浆 XOR 活性与体重指数（BMI；r=0.323，P<0.001）、腰围、血压以及包括丙氨酸氨基转移酶（r=0.694，P<0.001）、尿酸（r=0.249，P<0.001）、甘油三酯（r=0.312，P<0.001）、糖化血红蛋白、空腹血糖、胰岛素和 HOMA-R（r=0.238，P<0.001）在内的肝酶水平呈正相关，是胰岛素抵抗的标志物，与高密度脂蛋白胆固醇水平呈负相关。在逐步和多元回归分析中，BMI、吸烟以及丙氨酸氨基转移酶、尿酸、甘油三酯和 HOMA-R 水平是调整年龄和性别后血浆 XOR 活性的独立预测因子。
血浆 XOR 活性是一般人群代谢紊乱的一种新的生物标志物。
