The Association between Gene Polymorphism of TCF7L2 and Type 2 Diabetes in Chinese Han Population: A Meta-Analysis

Abstract

In recent years, it has been widely accepted that transcription factor 7-like 2 (TCF7L2) is associated with type 2 diabetes mellitus (T2DM) in multiple ethnic groups, especially its single nucleotide polymorphisms of rs7903146C/T, rs12255372G/T and rs290487T/C. However, the results previously obtained in Chinese Han population are often inconsistent. For clearing this issue, herein we performed meta-analysis based on the reports that can be found to assess the association. In the meta-analysis, Odds ratio (OR) and 95% confidence interval (95% CI) were calculated with random-effect model or fixed-effect model based on the heterogeneity analysis. The quality of included studies was evaluated by using the Newcastle-Ottawa Scale. The sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. In total, 20 case-control studies with 9122 cases of T2DM and 8017 controls were included. Among these case-control studies, we selected 13 ones on rs7903146 C/T, 5 ones on rs12255372 G/T, 8 ones on rs290487 T/C. The results indicated that rs7903146C/T polymorphism was significantly associated with T2DM (T vs. C, OR = 1.73, 95% CI = 1.39–2.16). There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88–3.56; C vs. T, OR = 1.08, 95% CI = 0.93–1.25). Subgroup analysis of different regions proved the relationship between rs7903146C/T polymorphism and T2DM risk in both the northern and the southern China. The association of rs290487 with T2DM was affected by body mass index, whereas the association of rs7903146 and rs290487 with T2DM was influenced neither by age nor by sex. In conclusion, this study indicated that the rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on T2DM risk in Chinese Han population, with rs12255372G/T and rs290487T/C polymorphisms showing no significant effect.

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil

“…First, we cannot rule out the possibility of population stratification bias when analyzing our samples, even though only white subjects were studied and both T2DM patients and non-diabetic subjects were recruited from the same hospital, thus reducing the risk of false-positive/negative associations due to this bias. Second, we did not perform a replication of the observed association in another sample from Southern Brazil, although our data is in agreement with the majority of studies performed in different populations (5)(6)(7)(8)31,(36)(37)(38)(39)(40) and also with another Brazilian study (23). Third, we only analyzed one SNP in the TCF7L2 gene.…”

“…The consistency in the data showing the association between TCF7L2 gene variants and risk for T2DM reported by many studies in different populations is believed to be a reliable indicative of a universal contribution of this gene to T2DM development (31), even though some studies have reported weak or no association with the disease, mainly in Asian populations (21,(32)(33)(34)(35). Thus, to date, around 10 meta-analyses evaluated the pooled effect of TCF7L2 rs7903146 SNP in T2DM risk (5)(6)(7)(8)31,(36)(37)(38)(39)(40).…”

“…Afterwards, this association has been replicated by numerous groups among different ethnicities, also with very low P values [reviewed in (4)]. Up to now, all of these studies firmly establish TCF7L2 gene as the strongest genetic risk factor for T2DM (4)(5)(6)(7)(8). Amongst the TCF7L2 variants, two intronic SNPs (rs12255372 and rs7903146) are the most closely associated with T2DM, and although both have showed a significant linkage disequilibrium (LD), the rs7903146 (C/T) variant seems to have the strongest effect in Caucasian populations (4,9).…”

IGF2BP2 rs11705701 polymorphisms are associated with prediabetes in a Chinese population: A population-based case-control study

“…A previous genome-wide association study demonstrated that the IRS1 rs7578326 polymorphism contributed to T2D susceptibility in European populations (23). In addition, the TCF7L2 rs12255372 was identified to be significantly associated with T2D (24), but a meta-analysis revealed no significant effect of rs12255372 on T2D risk in a Han Chinese population (25). The contradictory results between studies may be attributed to multiple factors, including different sample size, diverse genetic backgrounds, differing environmental factors and inclusion criteria.…”

Association of TCF7L2 gene polymorphisms with susceptibility to type 2 diabetes mellitus in a Chinese Hui population

“…It is estimated that the number of individuals affected by DM will increase to 300 million by the year 2025, with type 2 DM (T2DM) accounting for 90% of the diagnoses (King et al, 1998). The incidence and prevalence of T2DM are predicted to rapidly increase over the next decade owing to human longevity and the surge in obesity in many countries, particularly in China where T2DM will contribute almost 38 million patients to the global burden of DM by 2025 (Dou et al, 2013;Wang et al, 2013b). The global burden in 2010 was 285 million people, and the number of individuals affected by DM is projected to increase by 65% to 438 million by 2030 (Raza et al, 2013).…”