Department of Clinical Sciences, Lund University, Malmö, Sweden.
Diabet Med. 2011 Sep;28(9):1018-27. doi: 10.1111/j.1464-5491.2011.03359.x.
To test whether the TCF7L2 gene was associated with gestational diabetes, whether the association between TCF7L2 and gestational diabetes was independent of HLA-DQB1*0602 and islet cell autoantibodies, as well as maternal age, number of pregnancies, family history of diabetes and the HLA-DQB1 genotypes, and to test whether the distribution of HLA-DQB1 alleles was affected by country of birth.
We genotyped the rs7903146, rs12255372 and rs7901695 single nucleotide polymorphisms of the TCF7L2 gene in 826 mothers with gestational diabetes and in 1185 healthy control subjects in the Diabetes Prediction in Skåne Study. The mothers were also typed for HLA-DQB1 genotypes and tested for islet cell autoantibodies against GAD65, insulinoma-associated antigen-2 and insulin.
The heterozygous genotypes CT, GT and TC of the rs7903146 (T is risk for Type 2 diabetes), rs12255372 (T is risk for Type 2 diabetes) and rs7901695 (C is risk for Type 2 diabetes), respectively, as well as the homozygous genotypes TT, TT and CC of the rs7903146, rs12255372 and rs7901695, respectively, were strongly associated with gestational diabetes (P < 0.0001). These associations remained statistically significant after adjusting for maternal age, number of pregnancies, family history of diabetes and HLA-DQ genotypes and were independent of the presence of islet cell autoantibodies. No interaction was observed between TCF7L2 and HLA-DQB1*0602, which was shown to be negatively associated with gestational diabetes in mothers born in Sweden (P = 0.010).
The TCF7L2 was associated with susceptibility for gestational diabetes independently of the presence of HLA-DQB10602 and islet cell autoantibodies and other factors such as maternal age, number of pregnancies, family history of diabetes and other HLA-DQ genotypes. The HLA-DQB10602 was negatively associated with gestational diabetes in mothers born in Sweden.
检测 TCF7L2 基因是否与妊娠糖尿病相关，该相关性是否独立于 HLA-DQB1*0602 和胰岛细胞自身抗体、母亲年龄、妊娠次数、糖尿病家族史以及 HLA-DQB1 基因型，并检测 HLA-DQB1 等位基因的分布是否受出生地影响。
我们在斯堪尼亚糖尿病预测研究中对 826 例妊娠糖尿病母亲和 1185 例健康对照者的 TCF7L2 基因 rs7903146、rs12255372 和 rs7901695 单核苷酸多态性进行了基因分型。这些母亲还进行了 HLA-DQB1 基因型检测，并针对 GAD65、胰岛素瘤相关抗原-2 和胰岛素进行了胰岛细胞自身抗体检测。
rs7903146（T 等位基因是 2 型糖尿病的风险因素）、rs12255372（T 等位基因是 2 型糖尿病的风险因素）和 rs7901695（C 等位基因是 2 型糖尿病的风险因素）的杂合基因型 CT、GT 和 TC，以及 rs7903146、rs12255372 和 rs7901695 的纯合基因型 TT、TT 和 CC，均与妊娠糖尿病密切相关（P＜0.0001）。在调整了母亲年龄、妊娠次数、糖尿病家族史和 HLA-DQ 基因型后，这些关联仍然具有统计学意义，并且与胰岛细胞自身抗体的存在无关。未观察到 TCF7L2 与 HLA-DQB1*0602 之间存在相互作用，后者在出生于瑞典的母亲中与妊娠糖尿病呈负相关（P=0.010）。
TCF7L2 与妊娠糖尿病的易感性相关，与 HLA-DQB10602 和胰岛细胞自身抗体以及其他因素（如母亲年龄、妊娠次数、糖尿病家族史和其他 HLA-DQ 基因型）无关。HLA-DQB10602 与出生于瑞典的母亲的妊娠糖尿病呈负相关。
