Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population
Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population
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DOI：
10.1007/s00125-008-1039-3
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发表时间：
2008-07-01
期刊：
影响因子：
8.2
通讯作者：
Ji, L. N.
中科院分区：
文献类型：
--
作者：
Ren, Q.;Han, X. Y.;Ji, L. N.
目的/假设最近，在转录因子7样2（TCF 7 L2）基因的变异已被发现与2型糖尿病在不同的人群中一致。方法对100例中国2型糖尿病患者的TCF 7 L2基因外显子和内含子-外显子连接区进行直接测序，寻找新的变异，并对1,000例中国2型糖尿病患者的5个单核苷酸多态性（SNPs）进行基因分型。我们鉴定了6个SNPs（c.1，637 C> A; c.1，674 C> G; c.1，709 G> A; c.1，846 C> G; c.1，888 C> T;和c.1，876 T> G），其中3个导致非同义多态性（c.1，637 C> A，His -> Gln或Pro -> Thr; c.1，674 C> G，Pro）。Arg;和c. l，709G> A，Ala -> Thr）。除c.1，637 C> A外，其余均为罕见，在98个已测序个体中，c.1，637 C> A的次要A等位基因频率为0.23。在一项病例对照研究中，对其中一个新发现的SNPs（c.1，637 C> A）和四个已报道的SNPs（rs7903146、rs 12255372、rs 290487和rs3814573）进行了基因分型。这些SNP的等位基因和基因型频率在患者和对照组中的比较显示边缘（分别为p=0.063，OR 1.982，95%CI 1.128-3.485; p=0.071，OR 1.237，95%CI 0.983-1.557）。未发现rs 12255372、rs3814573、c.1，637 C> A与2型糖尿病相关（p=0.278-1.000）.结论/解释在目前的样本量下，我们在中国人群中没有发现任何TCF 7 L2编码序列中的突变，该突变赋予2型糖尿病的遗传风险，并且没有复制在其他人群中获得的一些主要阳性结果。
Aims/hypothesis Recently, variants in the transcription factor 7-like 2 (TCF7L2) gene have been found to be consistently associated with type 2 diabetes in different populations. In this study, we hypothesized that TCF7L2 also contributed to genetic susceptibility for type 2 diabetes in a Chinese population.MethodsWe looked for new variants by direct sequencing of all exons and intron-exon junctions of TCF7L2 in 100 Chinese type 2 diabetic patients, and then we genotyped five single nucleotide polymorphisms (SNPs) by Snapshot technology in 1,000 Chinese individuals.Results By sequencing, we identified six SNPs (c.1,637C > A; c.1,674C > G; c.1,709G > A; c.1,846C > G; c.1,888C > T; and c.1,876T > G), and three of them led to non-synonymous polymorphisms ( c.1,637C > A, His -> Gln or Pro -> Thr; c.1,674C > G, Pro. Arg; and c.1,709G > A, Ala -> Thr). All of them are rare except c.1,637C > A, which had a frequency of 0.23 for the minor A allele in 98 sequenced individuals. In a case-control study, one of the newly discovered SNPs (c.1,637C > A), together with four reported ones (rs7903146, rs12255372, rs290487 and rs3814573) were genotyped. Comparison between allele and genotype frequencies of these SNPs in patients and controls showed marginal (p=0.063, OR 1.982, 95% CI 1.128-3.485; p=0.071, OR 1.237, 95% CI 0.983-1.557, respectively). No association was found for rs12255372, rs3814573, c.1,637C > A and type 2 diabetes (p=0.278-1.000).Conclusions/interpretation With the current sample size, we did not find any mutation in the coding sequence of TCF7L2 that confers a genetic risk for type 2 diabetes in a Chinese population, and did not replicate some of the major positive results obtained in other populations.