Identification of MODY2 Gene Mutations and Its Clinical Correlation in Indian Females Affected with Gestational Diabetes

Abstract

Gestational Diabetes Mellitus (GDM) has a unique pathogenesis marked by an increased insulin resistance causing higher levels of blood glucose during pregnancy and it comes within the normal range as soon as the mother delivers. Similarly, another interesting form of diabetes is Maturity-onset diabetes of the young (MODY), which has a pure genetic basis and is caused due to the mutations in a specific gene. In the present study, we screened pregnant women and performed the genetic analysis for the three common MODY genes (GCK, HNF1A and HNF4A) in those diagnosed with GDM. Also, we estimated circulated serum levels of IL-6 and CRP in GDM and non-GDM women. Due to lack of funding we were able to perform both the analyses in a few samples. Collectively, in the present study we have identified three novel variants of the GCK, HNF1A and HNF4A genes. These variants were classified as damaging or likely pathogenic by the bioinformatics tools. These findings gives us a strong background to conduct functional studies to find out the effect of the mutations on function of the protein, specifically the GCK variant. Our findings also revealed augmented IL-6 levels in GDM samples as compared to the controls and these levels showed an association with obesity. This study gives an insight that GCK, HNF1A and HNF4A mutations might have a high prevalence amongst Indian females and that clinicians should be extra cautious while treating GDM. Moreover, Interleukin-6 is the cytokine which may be used as a biomarker for GDM. newline