No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach
No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach
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DOI：
10.1007/s00125-011-2235-0
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发表时间：
2011-10-01
期刊：
影响因子：
8.2
通讯作者：
Langenberg, C.
中科院分区：
文献类型：
--
作者：
Pfister, R.;Barnes, D.;Langenberg, C.
流行病学和实验证据表明，尿酸在2型糖尿病的病因学中起作用。使用孟德尔随机方法，我们调查了是否有证据表明血清尿酸在2型糖尿病的发生中起因果作用。我们检查了最近在全基因组关联研究中发现的8个常见变异的血尿酸升高等位基因的相关性，并在病例对照研究中总结了这一点与2型糖尿病的遗传评分，病例对照研究包括7,504名糖尿病患者和8,560名非糖尿病对照组。我们比较了观察到的效应大小和预期的效应大小：(1)非糖尿病对照组的遗传评分和尿酸水平之间的关系；(2)尿酸水平与糖尿病相关性的荟萃分析。遗传评分与尿酸水平呈线性相关，按三分位数计算的差异为12.2MU·mol/L(95%可信区间为9.3，15.1)。在遗传评分和潜在的混杂因素之间没有观察到显著的关联。没有观察到遗传评分与2型糖尿病之间的关联，OR值为0.99(95%可信区间0.94，1.04)/三分位数，与预期的(1.04[95%可信区间1.03，1.05])有显著差异(p=0.046)，这是基于观察到的尿酸差值和尿酸与糖尿病的关联1.21(95%可信区间1.14，1.29)。我们的结果不支持血尿酸在2型糖尿病发病中的因果作用，并限制了降尿酸药物在预防2型糖尿病中有效的期望。
Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes.We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association.The genetic score showed a linear association with uric acid levels, with a difference of 12.2 mu mol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p = 0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 mu mol/l.Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.