Department of Endocrinology and Diabetes, Medical School, University of Ioannina, 45110, Ioannina, Greece.
Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Hormones (Athens). 2018 Sep;17(3):359-365. doi: 10.1007/s42000-018-0047-z. Epub 2018 Jul 3.
Transcription factor 7-like 2 (TCF7L2) gene variants rs12255372 and rs7903146 have been consistently shown to raise genetic risk for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the possible role of these variants in the development of impaired glucose metabolism (IGM), including impaired fasting glucose (IFG) or T2DM, in patients with metabolic syndrome (MS).
The study population consisted of 228 patients with MS who were divided into two groups. The first group consisted of 148 patients with MS and IGM [39M/109F, 59.8 ± 14.6 (mean ± SD) years] and the second group of 80 patients with MS and normoglycemia (NGM) (16M/64F, 56.1 ± 15.8 years). The diagnosis of MS was based on the criteria proposed by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Anthropometric parameters including BMI and waist circumference were recorded and blood samples were obtained after overnight fasting for biochemical tests. The rs12255372 and rs7903146 TCF7L2 polymorphisms were genotyped in peripheral blood leucocytes.
Analysis of the distribution of the TCF7L2 polymorphic alleles revealed that the frequency of the T allele of the TCF7L2 variant rs12255372 was 38.2% in the study population, while the frequency of the T allele of the TCF7L2 rs7903146 variant was 35.3%. The T allele of the rs12255372 variant was more frequently present in patients with MS and IGM (48.3%) compared to patients with MS and NGM (19.4%, p < 0.001). Also, the T allele of rs7903146 was more frequently present in patients with MS and IGM (44.6%) compared to patients with MS and NGM (18.1%, p < 0.001). Logistic regression analysis followed and revealed that the presence of the T allele for both rs12255372 and rs7903146 TCF7L2 gene variants is a very powerful predictor of the presence of glucose disorders, increasing the risk more than fourfold in patients with MS and after adjustment for potential confounders, such as age, gender, BMI, and waist circumference (TCF7L2 rs12255372: Exp(B) 4.917, p < 0.001 and TCF7L2 rs7903146: Exp(B) 5.460, p < 0.001).
The presence of the rs12255372 and rs7903146 TCF7L2 gene variants plays an important role in the development of T2DM among individuals with MS. These findings support the notion that among subjects with MS, those who finally develop T2DM have a genetic predisposition to β-cell dysfunction.
转录因子 7 样 2（TCF7L2）基因变异 rs12255372 和 rs7903146 一直被证明可增加 2 型糖尿病（T2DM）的遗传风险。本研究旨在探讨这些变体在代谢综合征（MS）患者葡萄糖代谢受损（IGM），包括空腹血糖受损（IFG）或 T2DM 发展中的可能作用。
研究人群包括 228 名 MS 患者，他们分为两组。第一组包括 148 名 MS 和 IGM 患者[39M/109F，59.8±14.6（均值±标准差）岁]，第二组包括 80 名 MS 和正常血糖（NGM）患者[16M/64F，56.1±15.8 岁]。MS 的诊断基于美国心脏协会/国家心肺血液研究所（AHA/NHLBI）科学声明提出的标准。记录了包括 BMI 和腰围在内的人体测量参数，并在过夜禁食后采集血液样本进行生化检查。在周围血白细胞中对 TCF7L2 基因 rs12255372 和 rs7903146 多态性进行了基因分型。
TCF7L2 多态性等位基因分布分析显示，研究人群中 TCF7L2 变体 rs12255372 的 T 等位基因频率为 38.2%，而 TCF7L2 rs7903146 变体的 T 等位基因频率为 35.3%。rs12255372 变体的 T 等位基因在 MS 和 IGM 患者（48.3%）中比在 MS 和 NGM 患者（19.4%）中更为常见（p<0.001）。此外，rs7903146 的 T 等位基因在 MS 和 IGM 患者（44.6%）中比在 MS 和 NGM 患者（18.1%）中更为常见（p<0.001）。随后进行了 logistic 回归分析，结果表明，TCF7L2 基因 rs12255372 和 rs7903146 两个变体的 T 等位基因的存在是葡萄糖紊乱存在的一个非常有力的预测因子，在调整了年龄、性别、BMI 和腰围等潜在混杂因素后，MS 患者的患病风险增加了四倍以上（TCF7L2 rs12255372：Exp（B）4.917，p<0.001；TCF7L2 rs7903146：Exp（B）5.460，p<0.001）。
rs12255372 和 rs7903146 TCF7L2 基因变体的存在在 MS 患者 2 型糖尿病的发展中起重要作用。这些发现支持了这样一种观点，即在 MS 患者中，最终发展为 2 型糖尿病的患者β细胞功能障碍存在遗传易感性。
