Association between transcription factor 7-like 2 genetic polymorphisms and development of type 2 diabetes in a Chinese population

Abstract

ABSTRACT. We conducted a hospital-based case-control study to evaluate the relationship between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and type 2 diabetes mellitus risk in a Chinese population. Genotyping of TCF7L2 rs7903146 was carried out using the polymerase chain reaction-restriction fragment length polymorphism method. A chi-square test revealed a statistically significant difference between the distributions of rs7903146 genotypes in type 2 diabetes mellitus patient and control groups (chi-square = 10.49, P = 0.005). Using unconditional logistic regression analysis, we observed that the TT genotype of this polymorphism was significantly correlated with increased risk of developing type 2 diabetes mellitus compared to the CC genotype [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.33-4.04]. Furthermore, we found that the rs7903146 sequence variation was also significantly associated with susceptibility to this disease under dominant (OR = 1.58, 95%CI = 1.09-2.28) and recessive models (OR = 2.11, 95%CI = 1.25-3.62). We conclude that the TCF7L2 rs7903146 genetic polymorphism is independently associated with the risk of developing type 2 diabetes mellitus under co-dominant, dominant, and recessive models.

Association of TCF7L2 mutation and atypical diabetes in a Uruguayan population

“…Beyond the ethnic influence that has also been found in other studies of rs12255372 and rs7903146[ 17 - 25 ], this study showed that the association of rs12255372 with diabetes was increased when the population was reclassified as subgroups of case types and only the classical T2D patients were compared with controls. This finding suggests the importance of taking into consideration the existence of an atypical group, which could serve to obscure the real association of SNPs in the TCF7L2 gene.…”

“…Diabetes mellitus is a complex disease, in which genetic and environmental factors are interweaved. After the discovery of TCF7L2 as a key player in T2D etiology, several works in multiethnic populations identified two main SNPs in this gene, rs12255372 and rs7903146, and characterized them as the most relevantly associated to T2D[ 9 , 10 , 17 , 21 ]. In our previous works[ 3 - 5 ], we reclassified patients who are clinically diagnosed as T2D into two subgroups, representing the classical and atypical cases, as described in the Materials and Methods section.…”

“…The TCF7L2 gene is located on chromosome 10q25 and is composed of two major domains: a catenin-binding domain (exon 1) and a central DNA-binding HMG domain (exons 10 and 11). Variations in this gene have been consistently associated with T2D in studies of different populations, namely those of Caucasian, Asian and African origin, and specifically involving two intronic single nucleotide polymorphisms (SNPs): rs12255372 (G>T) and rs7903146 (C>T)[ 17 - 25 ]. For rs12255372, homozygous carriers of the rare T allele produce 2.5-fold higher levels of TCF7L2 transcript than wild-type carriers, while heterozygous carriers of both alleles produce 1.5-fold higher[ 26 ].…”

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

“…This phenomenon might be due to impaired insulin secretor and/or insulinotropic effects of incretins rather than an insulin resistance [ 21 , 22 ]. Recently, several case-control studies focused on the relationship of TCF7L2 rs7903146 C>T with the development of T2DM in China [ 7 , 10 , 11 ]. The results of a meta-analysis also indicated that TCF7L2 rs7903146 C>T variants might confer an increased risk to T2DM in Chinese population [ 13 ].…”