CNRS UMR 8090, Institute of Biology, Genomics and Molecular Physiology of Metabolic Diseases, Lille, France.
Mol Genet Metab. 2010 May;100(1):77-82. doi: 10.1016/j.ymgme.2010.01.001. Epub 2010 Jan 15.
The C-allele of rs13266634 located in SLC30A8 (ZNT8) has been strongly associated with decreased insulin release and with type 2 diabetes (T2D) susceptibility in some but not all studies. To shed further light on this issue, we performed a meta-analysis of the association between rs13266634 and T2D in different ethnic groups and assessed the relationships between SLC30A8 genotypes and some properties of isolated human islets.
From 32 original articles, a total of 77,234 control individuals and 44,945 subjects with T2D were studied in meta-analysis. To assess the relationships between SLC30A8 genotype and islet cell phenotype, insulin secretion in response to glucose, glucose plus arginine and glucose plus glibenclamide was determined in pancreatic islets isolated from 82 multiorgan donors genotyped for the rs13266634 polymorphism. Quantitative expression of SLC30A8, Insulin and Glucagon mRNA was also measured.
Overall, each SLC30A8 risk allele was associated with a 14% increased risk for T2D (P=2.78 x 10(-34)). The population risk of T2D attributable to this polymorphism was estimated at 9.5% in Europeans and 8.1% in East Asians. Basal and stimulated insulin secretion from human islets as well as islet expressions of SLC30A8, Insulin and Glucagon were not affected by the presence of the polymorphism. However, SLC30A8 expression was positively correlated with Insulin (r=0.75, P=6.43 x 10(-6)) and Glucagon (r: 0.70, P=4.89 x 10(-5)) levels.
The SLC30A8 rs13266634 polymorphism is among the most confirmed genetic markers of T2D in Europeans and East Asians. In isolated human islets, the risk C-allele does not affect ex-vivo insulin secretion and SLC30A8 expression, which is correlated with that of insulin and glucagon.
位于 SLC30A8（ZNT8）的 rs13266634 等位基因 C 与胰岛素释放减少和 2 型糖尿病（T2D）易感性有关，但并非所有研究均如此。为了进一步阐明这个问题，我们对不同种族人群中 rs13266634 与 T2D 的相关性进行了荟萃分析，并评估了 SLC30A8 基因型与分离的人胰岛某些特性之间的关系。
从 32 篇原始文章中，对荟萃分析共纳入了 77234 名对照个体和 44945 名 T2D 患者。为了评估 SLC30A8 基因型与胰岛细胞表型之间的关系，我们对 82 名多器官供者进行了基因型分析，这些供者的 rs13266634 多态性，以确定葡萄糖、葡萄糖加精氨酸和葡萄糖加格列本脲刺激下的胰岛素分泌。还测量了 SLC30A8、胰岛素和胰高血糖素 mRNA 的定量表达。
总体而言，SLC30A8 风险等位基因的每个个体患 T2D 的风险增加 14%（P=2.78×10(-34)）。该多态性导致欧洲人群 T2D 的人群风险估计为 9.5%，东亚人群为 8.1%。来自人胰岛的基础和刺激胰岛素分泌以及 SLC30A8、胰岛素和胰高血糖素的胰岛表达不受该多态性的影响。然而，SLC30A8 的表达与胰岛素（r=0.75，P=6.43×10(-6)）和胰高血糖素（r：0.70，P=4.89×10(-5)）水平呈正相关。
SLC30A8 rs13266634 多态性是欧洲人和东亚人 2 型糖尿病最具确认的遗传标记之一。在分离的人胰岛中，风险 C 等位基因不影响体外胰岛素分泌和 SLC30A8 的表达，其与胰岛素和胰高血糖素的表达相关。
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