Significant ACE Gene Haplotype Stipulates Development of Type 2 Diabetes in Women with Gestational Diabetes Mellitus

Abstract

Introduction: Angiotensin-converting enzyme (ACE) plays a key role in glucose and insulin regulation, and in the onset of diabetes. ACE gene polymorphisms A240T, C1237T, G2350A and I/D located in the promoter, coding and non-coding regions have been studied in both type-2 diabetes and gestational diabetes mellitus (GDM). However, their impact on the development of type-2 diabetes post GDM remains unknown, especially in under-represented population. Aim: We examined possible associations and networking between ACE gene polymorphism susceptibility / protection towards/against progression of type-2 diabetes post GDM in North Indian women. Methods: Two hundred and twenty four women (n = 224) were recruited in this study and genotyped for four ACE gene polymorphisms using polymerase chain reaction (PCR), followed by digestion through restriction endonuclease enzymes. Results: Study results suggest a significant association of ACE genes SNPs A240T, C1237T, G2350A and I/D haplotype with GDM cases progressing to type-2 diabetes later in life (P =.02). Individuals possessing haplotype “CAAI” derived from these SNPs had a 3.65 fold increased risk of type-2 diabetes development in GDM cases later in life relative to other haplotypes. Conclusion: Due to its pivotal role in the pathogenesis of both diseases, the current finding might be of future therapeutic value. Larger-scale studies are required to confirm this novel finding in multi-ethnic populations.