Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.
Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.
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DOI：
10.1038/ki.2013.353
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发表时间：
2014-03
影响因子：
19.6
通讯作者：
Merriman TR
中科院分区：
文献类型：
--
作者：
Hughes K;Flynn T;de Zoysa J;Dalbeth N;Merriman TR
血清尿酸盐升高可独立于其他危险因素预测慢性肾脏疾病。黄嘌呤氧化酶抑制剂的使用与肾功能改善一致。这是否是由于血清尿酸盐减少或黄嘌呤氧化酶或其他生理机制的氧化剂的生产减少仍然没有解决。在这里，我们应用孟德尔随机化，一种统计遗传学方法，允许在存在潜在混杂的情况下解开因果关系，以确定通过遗传调节肾排泄降低血清尿酸盐是否有益于肾功能，使用来自社区和心脏病研究中动脉粥样硬化风险的7979例患者的数据。采用两阶段最小二乘法进行孟德尔随机化，以血清尿酸盐作为暴露量，尿酸转运蛋白遗传风险评分作为工具变量，估计肾小球滤过率和血清肌酐作为结局。在男性中，遗传风险评分增加与肾功能显著改善相关，但在女性中则无关。个体遗传变异的分析显示，在孟德尔随机化模型中，与血清尿酸盐相关的效应量与肾功能相关的效应量不相关。这与这些遗传变异在提高血清尿酸盐中的生理作用与肾功能改善直接相关的可能性一致。黄嘌呤氧化酶抑制剂对肾功能的保护作用机制尚需进一步研究。
Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.
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影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
影响因子：
19.6
作者：
通讯作者：
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葡萄糖激酶调节蛋白（GCKR）基因rs4425043多态性与中国女性超重和肥胖相关
影响因子：
1.9
作者：
Cao, Feifei;Wang, Xiaofeng;Jin, Li
通讯作者：
Jin, Li
影响因子：
3.7
作者：
Lyngdoh T;Vuistiner P;Marques-Vidal P;Rousson V;Waeber G;Vollenweider P;Bochud M
通讯作者：
Bochud M
DOI：
10.2215/cjn.01580210
发表时间：
2010-08-01
影响因子：
9.8
作者：
Goicoechea, Marian;Garcia de Vinuesa, Soledad;Luno, Jose
通讯作者：
Luno, Jose