Identification of Mody Gene Polymorphisms in Asian Indians Affected with Gestational Diabetes-First Report from India

Presentation Number: SAT 596
Date of Presentation: April 1st, 2017

Sujeet Jha*1, Samreen Siddiqui1, Swati W Pandit1, Amit Bhargava1, Manju Panda1 and Shweta Dubey2
1Max Healthcare Inst Ltd, New Delhi, India, 2Amity University, Noida, India

Abstract

Objective:

Maturity onset diabetes of the young (MODY) is an autosomal inherited form of diabetes where gene mutations lead to pancreatic β cell dysfunction. At least 13 different subtypes are known to cause MODY. Individuals with mutations in MODY genes can also present with gestational diabetes mellitus (GDM). Precise molecular analysis of MODY gene variants in GDM cases is essential because it can have implications in management of diabetes in pregnancy and is crucial to the health of both mother and the fetus. However, the exact association between MODY gene variants and GDM is not established. We undertook this study to determine whether MODY gene polymorphisms induce susceptibility to GDM in pregnant Indian females.

Research Design & Methods

Of the 68 pregnant females screened, 25 were randomly selected, based on new screening criteria of BMI<25Kg/m2 and fasting blood glucose ≥5.5 mmol/L (99 mg/dL). Saliva from this GDM subset was analyzed for mutations in 3 common MODY genes (HNF1a, HNF4a and GCK). Bioinformatics tools were used to predict the outcome of identified gene mutations.

Results

4 novel mutations including 2 missense and 2 splice-site mutations were identified on the GCK (c.1030G>T (p.Asp344Tyr)), HNF1a (c.1501+1G>A, c.224G>A (p.Arg75Lys)) and HNF4a (p.Gln294Arg) genes, respectively. Further analysis revealed that 72% of the total cohort had HNF4a gene mutations, 56% had HNF1a gene mutations and 36% had GCK mutations.

Conclusions

We report 4 novel variations of MODY genes in Indian GDM population subset. Our results suggest that there might be a high prevalence of MODY amongst Indian females presenting with GDM, than previously predicted. Females with clinical features of MODY should be screened for the aforementioned genetic mutations during pregnancy.

 

Nothing to Disclose: SJ, SS, SWP, AB, MP, SD