Association of common variants of and with gestational diabetes mellitus in West Bengal, India.

The genetic etiology of gestational diabetes mellitus (GDM) was suggested to overlap with type-2 diabetes(T2D). Transcription factor 7-like 2 () and Proprotein Convertase Subtilisin/Kexin type 2 () are T2D susceptibility genes of the insulin synthesis/processing pathway. We analyzed associations of and variants with GDM risk and evaluated their potential impact on impaired insulin processing in an eastern Indian population. The study included 114 GDM (case) and 228 non-GDM pregnant women (control). rs7903146, rs4132670, rs12255372 of , and rs2269023 of were genotyped by PCR-RFLP, and genotype distributions were compared between case and control. Fasting serum proinsulin and C-peptide levels were measured by ELISA and the Proinsulin/C-peptide ratio was considered an indicator of proinsulin conversion. Significantly higher frequency of risk allele (T) of rs12255372 ( = 0.02, OR = 2.0, 95%CI = 1.11-3.64) and rs4132670 ( = 0.002, OR = 2.26, 95%CI = 1.32-3.87) of was found in GDM cases than non-GDM controls; TT genotype was associated with significantly increased disease risk. In rs7903146 () and rs2269023 (), although the frequency of risk allele (T) was not significantly higher in cases than controls, an association of TT for both variants remained significant with higher GDM risk in the recessive model. Increased serum pro-insulin and proinsulin:c-peptide ratio was found in GDM than non-GDM women and the phenomenon showed significant association with careers of risk alleles for variants. In conclusion, and variants are related to GDM risk in the studied population and hence may serve as potential biomarkers for assessing the disease risk. variants contribute to impaired insulin processing.