Endocrine Abstracts

Introduction: Genetic predisposition with environmental factors plays a significant role in the development of type 2 diabetes mellitus. Among the diabetogenic genes, the transcription factor 7-like 2 (TCF7L2), a member of the Wnt signalling pathway remains the strongest genetic determinant of type 2 diabetes risk in humans. Our aim was to investigate whether TCF7L2 variants that have previously been associated with type2 diabetes would also confer risk for gestational diabetes mellitus in South India population.

Materials and methods: In 166 unrelated women (117 women with gestational diabetes mellitus and 49 non-diabetic control subjects) DNA extraction was done using Gentra Puregene Blood Method during the period January 2012–April 2013. The primers were validated by Sanger sequencing (3130 Genetic Analyzer). We genotyped three TCF7L2 polymorphisms (rs7903146, rs12255372, and rs4506565) using TaqMan allelic discrimination assay in our Molecular Laboratory.

Results and discussion: In a small South Indian population, we have found that the odds ratio (OR) of TCF7L2 polymorphisms rs4506565, rs7903146, and rs12255372 were (OR=3.75 (95% CI 0.75–18.53), P=0.08), (OR=1.77 (95% CI 0.503–6.263), P=0.37), and (OR=1.40 (95% CI 0.24–8.11), P=0.70) respectively, when compared with controls for the occurrence of gestational diabetes. The common variants of TCF7L2 (rs7903146,rs12255372, and rs4506565) have been shown to be associated with diabetes mellitus in European (Cauchi et al. 2007) and Asian population (Chandak et al. 2006, Alami et al. 2012) (OR=1.3–1.9). The association of GDM with these TCF7L2 variants has varied in different populations, in Mexican Americans (OR=2.49 (95% CI 1.17–5.31), P=0.018), Arab women (OR=2.370, (95% CI 1.010–5.563, P=0.047), and Scandinavian women (OR=1.49 (95% CI 1.28–1.75), P=0.049).

Conclusion: The TCF7L2 polymorphism rs4506565 showed a trend towards association with gestational diabetes, when compared to the other two common polymorphisms in TCF7L2 (rs7903146 and rs12255372). However, to confirm our findings further studies need to be performed in a larger population.