TCF7L2 rs290481 T>C polymorphism is associated with an increased risk of type 2 diabetes mellitus and fasting plasma glucose level

Abstract

Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene may be key agents in the etiology of type 2 diabetes mellitus (T2DM). In the present case-control study, we aimed to assess the possible relationship of TCF7L2 polymorphisms with T2DM and determine the effect of TCF7L2 polymorphisms on the level of fasting plasma glucose (FPG) in Eastern Chinese Han subjects. The TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms were genotyped by SNPscan genotyping assays in 502 subjects with T2DM and 782 non-diabetic controls. After adjusting for age, gender, drinking, smoking and body mass index (BMI), the association of TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms with T2DM was determined. We found that TCF7L2 rs290481 T>C polymorphism increased the susceptibility of T2DM in the overall comparison. In subgroup analyses by age, sex, BMI, alcohol use and smoking status, a significantly increased risk of T2DM was also found in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. The relationship of TCF7L2 rs290481 T>C polymorphism with the biochemistry characteristics in controls was also assessed. We found that TCF7L2 rs290481 T>C polymorphism significantly increased the level of FPG in controls. Our findings suggest that TCF7L2 rs290481 T>C polymorphism is associated with T2DM in Eastern Chinese Han population and links to variations in FPG level. In addition, these relationships are more pronounced in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. A comprehensive fine-mapping study with functional investigation is needed to confirm or refute these potential correlations.

Association of metabolism‐related genes polymorphisms with adenocarcinoma of the oesophagogastric junction: Evidence from 2261 subjects

“…In this SNP, we found that the rs290481TC and TC/CC genotype of TCF7L2 gene is relevant to increased susceptibility and progress of AEG. In additional, we also found that the potential association was more significant in BMI ≥24 kg/m 2 , which was in line with the findings of those studies mentioned above …”

“…In additional, we also found that the potential association was more significant in BMI ≥24 kg/m 2 , which was in line with the findings of those studies mentioned above. 14,26,27 In this study, the relationship between rs1799817 G > A (NM_000208.2:c.3255C > T) polymorphism in the INSR gene and AEG risk was also explored. We found that INSR rs1799817 G > A polymorphism might confer the risk to AEG.…”

“…TCF7L2 rs290481 (T > C) locus is located in intron 13 (NC_000010.10:g.114923825C > T). Zhu et al reported that rs290481 polymorphism in TCF7L2 gene increased the susceptibility of T2D and linked to the level of fasting glucose. A previous study evaluated the potential association between TCF7L2 rs290481 variants and cancer risk in Chinese patients with T2D.…”

The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

“…The transcription factor 7-like 2 ( TCF7L2 ) gene plays an important role in various processes, including the activation of target genes in the Wnt signalling pathway [ 34 ], pancreatic β cell proliferation, and glucose homeostasis [ 35 ]. In addition, TCF7L2 is the most significant and consistently replicated gene associated with an increased risk of T2DM [ 34 ].…”

Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China

“…For example, evidence for the linkage of Chromosomes 2 and 5 with T2DM was found in females only [ 23 ]. Female-specific associations with T2DM were demonstrated for multiple genes, such as CDKN2A/2B , KCNJ11 , and TCF7L2 [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Male-specific associations with T2DM also involved various genes, such as TCF7L2 , ELMO1 , and BCL11A [ 31 , 32 , 33 , 34 ].…”