Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population
Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population
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DOI：
10.1007/s00125-006-0502-2
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发表时间：
2007-01-01
期刊：
影响因子：
8.2
通讯作者：
Yajnik, C. S.
中科院分区：
文献类型：
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作者：
Chandak, G. R.;Janipalli, C. S.;Yajnik, C. S.
目的和假设在任何一个国家中，印度有最多的糖尿病患者，但印度2型糖尿病的遗传基础知之甚少。转录因子7样2基因（TCF 7 L2）中常见的非编码变体最近与欧洲人群2型糖尿病风险增加密切相关。我们调查了TCF 7 L2变异是否也与印度人群中的2型糖尿病有关。材料和方法我们通过对3个单核苷酸多态性（SNPs）进行测序对2型糖尿病患者（n = 955）和种族匹配的对照组（n = 399）进行基因分型。结果TCF 7 L2基因的rs7903146、rs 12255372和rs 4506565位点多态性与TCF 7 L2基因的多态性有很强的相关性，其中rs 12255372位点多态性与TCF 7 L2基因的多态性有很强的相关性（比值比[OR] 1.50 [95% CI = 1.24-1.82]，p = 4.0 x 10（-5）），rs 4506565（OR 1.48 [95% CI = 1.24-1.77]，p = 2.0 x 10（-5）和rs7903146（OR 1.46 [95% CI = 1.22-1.75]，p = 3.0 x 10（-5））。当纯合子而不是杂合子时，所有三种变体均显示出相对风险增加，其中rs 12255372的风险最高（OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]）。我们发现TCF 7 L2基因型与诊断时的年龄、BMI或WHR无关，但rs 12255372的风险基因型与较高的空腹血糖相关（p = 0.001），2小时血糖升高（p = 0.0002）和更高的稳态模型评估胰岛素抵抗结论我们在印度受试者中的研究重复了TCF 7 L2变异与其他人群中2型糖尿病的强相关性。这也提供了证据表明，TCF 7 L2的变化可能通过影响胰岛素分泌和胰岛素抵抗在2型糖尿病的发病机制中起着至关重要的作用。TCF 7 L2是决定2型糖尿病易感性的重要基因，它跨越了种族界限。
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.