TCF7L2基因中的常见变异与印度人群中的2型糖尿病密切相关。
Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population.
作者信息
Chandak G R, Janipalli C S, Bhaskar S, Kulkarni S R, Mohankrishna P, Hattersley A T, Frayling T M, Yajnik C S
机构信息
Genome Research Group, Centre for Cellular and Molecular Biology, Hyderabad, India.
出版信息
Diabetologia. 2007 Jan;50(1):63-7. doi: 10.1007/s00125-006-0502-2. Epub 2006 Nov 9.
AIMS AND HYPOTHESIS
India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population.
MATERIALS AND METHODS
We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2.
RESULTS
We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24-1.82], p = 4.0 x 10(-5)), rs4506565 (OR 1.48 [95% CI = 1.24-1.77], p = 2.0 x 10(-5)) and rs7903146 (OR 1.46 [95% CI = 1.22-1.75], p = 3.0 x 10(-5)). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects.
CONCLUSIONS
Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.
目的与假设
印度是糖尿病患者人数最多的国家，但对印度2型糖尿病的遗传基础了解甚少。转录因子7样2基因（TCF7L2）中的常见非编码变异最近与欧洲人群中2型糖尿病风险增加密切相关。我们调查了TCF7L2变异是否也与印度人群的2型糖尿病相关。
材料与方法
我们通过对TCF7L2中的三个单核苷酸多态性（SNP）（rs7903146、rs12255372和rs4506565）进行测序，对2型糖尿病患者（n = 955）和种族匹配的对照受试者（n = 399）进行基因分型。
结果
我们观察到所有多态性均有很强的相关性，包括rs12255372（优势比[OR]1.50[95%置信区间=1.24 - 1.82]，p = 4.0×10⁻⁵）、rs4506565（OR 1.48[95%置信区间=1.24 - 1.77]，p = 2.0×10⁻⁵）和rs7903146（OR 1.46[95%置信区间=1.22 - 1.75]，p = 3.0×10⁻⁵）。当为纯合子而非杂合子时，所有三个变异的相对风险均增加，rs12255372的风险最强（OR 2.28[95%置信区间=1.40 - 3.72]对比OR 1.43[95%置信区间=1.11 - 1.83]）。我们发现TCF7L2基因型与诊断年龄、体重指数或腰臀比无关，但rs12255372处的风险基因型与非糖尿病受试者较高的空腹血糖（p = 0.001）、较高的2小时血糖（p = 0.0002）和较高的胰岛素抵抗稳态模型评估（HOMA - R；p = 0.012）相关。
结论
我们在印度受试者中的研究重复了TCF7L2变异与其他人群中2型糖尿病的强相关性。它还提供了证据表明TCF7L2的变异可能通过影响胰岛素分泌和胰岛素抵抗在2型糖尿病发病机制中起关键作用。TCF7L2是决定2型糖尿病易感性 的一个重要基因，且不受种族界限的限制。
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