Genome-Wide Association Study (GWAS)-Derived Type 2 Diabetes Risk Variants in Gestational Diabetes Mellitus: Evidence...

Area of Science:

• Genetics
• Endocrinology
• Obstetrics

Background:

• Gestational diabetes mellitus (GDM) is characterized by hyperglycemia during pregnancy.
• GDM and type 2 diabetes mellitus (T2DM) share underlying mechanisms like insulin resistance.
• Genetic predisposition to T2DM may influence GDM susceptibility.

Purpose of the Study:

• To investigate the association between specific T2DM-related genetic variants and GDM risk.
• To examine three genome-wide association study (GWAS)-identified T2DM variants (AP3S2 rs2028299, ST6GAL1 rs16861329, VPS26A rs1802295) in a North Indian population.
• To assess GDM susceptibility in pregnant women based on these genetic markers.

Main Methods:

• An observational case-control study involving 69 GDM cases and 69 matched controls from North India.
• GDM diagnosis was confirmed using the Diabetes in Pregnancy Study Group India (DIPSI) criteria with a 75g oral glucose tolerance test (OGTT).
• Genotyping of the selected variants was performed using polymerase chain reaction (PCR) and Sanger sequencing.

Main Results:

• Women with GDM exhibited higher triglyceride and VLDL levels.
• A family history of T2DM was significantly associated with increased GDM risk (p=0.024).
• The AP3S2 A allele (rs2028299) showed a 2.26-fold increased GDM risk (OR=2.26, p=0.005). The ST6GAL1 CT genotype (rs16861329) and T allele were also associated with higher GDM risk (OR=2.30, p=0.017 and OR=1.95, p=0.018, respectively).

Conclusions:

• Specific variants rs2028299 (AP3S2) and rs16861329 (ST6GAL1) are significantly associated with GDM in this North Indian cohort.
• These findings suggest a potential overlap in genetic susceptibility between GDM and T2DM.
• Further functional studies and larger, multi-center cohorts are required to elucidate biological mechanisms and confirm generalizability.