Significant ACE Gene Haplotype Stipulates Development of Type 2 Diabetes in Women with Gestational Diabetes Mellitus
Parul Aggarwal
Department of Biophysics, AIIMS, New Delhi, India and Dasman Diabetes Institute, Kuwait
Nutan Agarwal
Department of Obstetrics and Gynyaecology, AIIMS, New Delhi, India
Krishna Dalal
Department of Obstetrics and Gynyaecology, AIIMS, New Delhi, India
Mohamed M. Jahromi *
Dasman Diabetes Institute, Kuwait
*Author to whom correspondence should be addressed.
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.
Keywords: Haplotype, GDM, type-2 diabetes, Single Nucleotide Polymorphism (SNP), ACE