TCF7L2 gene rs7903146 and rs12255372 polymorphism is not associated with gestational diabetes in Bangladeshi women

Abstract Background Pathogenesis of gestational diabetes mellitus (GDM) is comparable to Type 2 diabetes mellitus (T2D), as both conditions are characterized by failure to sufficiently increase insulin secretion against escalating insulin resistance. TCF7L2 is a potential locus for development of T2DM with two important SNPs rs7903146 and rs12255372. Alterations in the activity of TCF7L2 in beta-cells in carriers of at-risk allele may lead to development of T2DM. Our goal was to evaluate the association between these two SNPs and GDM in the population of Bangladesh. Aim To explore the association of rs7903146 and rs12255372 polymorphism of TCF7L2 gene with GDM in Bangladeshi women. Method This study enrolled 110 pregnant mothers consecutively among which 38 women had GDM and 72 women had normal glucose tolerance (NGT) irrespective of their gestational age on the basis of WHO 2013 criteria. Genotyping of TCF7L2 rs7903146 and rs12255372 variants was done by Sanger’s sequencing and analyzed using sequencing analysis software. SNPStats was used to examine the associations of SNPs with GDM under various genetic models. For statistical significance, a p -value of < 0.05 was considered. Result The genotype frequencies of rs7903146-CC/CT/TT in GDM group and control group were 61%/68%, 39%/26%, 0/6% and those of rs12255372-GG/GT/TT were 84%/74%, 16%/18%, 0%/1% respectively. Association of these SNPs with GDM was tested under different genetic models which revealed no significant ( p > 0.05) association. The linkage disequilibrium (LD) analysis of TCF7L2 rs7903146 and rs12255372, (D = 0.059, D’ = 0.623, r 2 = 0.23; p < 0.001), showed no LD between the variants. Age and fasting insulin were found to be independent predictors of GDM in univariate analysis. rs7903146 CT genotype confers 1.68 times risk of development of GDM although it was insignificant. However, multivariate logistic regression analysis did not identify any independent predictor of GDM ( p > 0.05). Conclusion This study demonstrates no significant association between TCF7L2 polymorphisms and GDM in Bangladeshi women, highlighting the need for larger, more comprehensive studies.