Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion
Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion
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DOI：
10.1007/s00125-007-0656-6
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发表时间：
2007-06-01
期刊：
影响因子：
8.2
通讯作者：
Laakso, M.
中科院分区：
文献类型：
--
作者：
Wang, J.;Kuusisto, J.;Laakso, M.
目的/假设我们研究了转录因子7样2（TCF 7 L2）基因变异与以下因素的关系：（1）芬兰糖尿病预防研究中的偶发糖尿病（DPS，研究I）;（2）2型糖尿病和葡萄糖调节受损（即IGT或IFG）在横断面研究中（研究二）;和（3）胰岛素分泌，2型糖尿病先证者后代TCF 7 L2的胰岛素敏感性和脂肪组织表达（III）：研究对象和方法纳入了507名IGT患者，他们被随机分配到对照组和干预组，平均随访3.9年，以监测糖尿病的进展。研究II是一项以人群为基础的横断面研究，从芬兰东部库奥皮奥的人群中随机选择了1,766名50-70岁的男性。研究III包括238名2型糖尿病患者的非糖尿病后代。结果对照组rs 12255372和rs7903146的TT基因型与2.85倍的糖尿病发病风险显著相关（95%CI 1.17-6.95，p=0.021），而干预组与此无关。在研究II中，对于糖尿病受试者与正常血糖受试者的比较，TT基因型受试者的校正比值比为3.40（1.45-7.97，p=0.005）。rs 12255372的T等位基因与胰岛素分泌减少显著相关（研究II、III）。TCF 7 L2在脂肪组织中的表达在TT风险基因型rs 12255372和rs7903146的受试者中倾向于较低。结论/解释在DPS和一项单独的基于人群的横断面研究中，TCF 7 L2的rs 12255372变异与2型糖尿病的发病相关。胰岛素分泌受损可能是我们发现的主要原因。
Aims/hypothesis We investigated the association of variants of the transcription factor 7-like 2 (TCF7L2) gene with: (1) incident diabetes in the Finnish Diabetes Prevention Study (DPS, Study I); (2) type 2 diabetes and impaired glucose regulation (i.e. IGT or IFG) in a cross-sectional study (Study II); and (3) insulin secretion, insulin sensitivity and adipose tissue expression of TCF7L2 in offspring of type 2 diabetic probands (III).Subjects and methods Study I (the DPS) included 507 individuals with IGT who were randomly allocated to control and intervention groups and followed for an average of 3.9 years to monitor for progression to diabetes. Study II was a population-based cross-sectional study of 1,766 men, aged 50-70 years, randomly selected from the population of Kuopio, eastern Finland. Study III included 238 non-diabetic offspring of patients with type 2 diabetes. Genotyping of rs12255372 and rs7903146 of TCF7L2 was carried out.Results In the DPS, the TT genotype of rs12255372 was significantly associated with an adjusted 2.85-fold risk (95% CI 1.17-6.95, p=0.021) of incident diabetes in the control group, but not in the intervention group. In Study II, the adjusted odds ratio in subjects with the TT genotype was 3.40 (1.45-7.97, p=0.005) for the comparison of diabetic subjects with normoglycaemic subjects. The T allele of rs12255372 was significantly associated with decreased insulin secretion (Studies II, III). Expression of TCF7L2 in adipose tissue tended to be lower in subjects with the TT risk genotypes of rs12255372 and rs7903146.Conclusions/interpretation The variant of rs12255372 of TCF7L2 was associated with incident type 2 diabetes in the DPS and in a separate population-based cross-sectional study. Impaired insulin secretion is likely to be the main cause for our findings.