Genetic Screening of Genome-Wide Association Studies-Derived Risk Loci for Type 2 Diabetes Mellitus: Confirmation in the North Indian population.

OBJECTIVES

This case-control study investigated the association of three novel South Asian genome-wide association studies (GWAS)-derived type 2 diabetes mellitus (T2DM) susceptibility gene polymorphisms in the North Indian population.

METHODS

The study was conducted at King George's Medical University, Lucknow, India, between January 2022 and December 2023. Three single nucleotide polymorphisms (SNPs) were genotyped: rs2028299 (C>A) near the AP3S2 gene, rs1802295 (C>T) near the VPS26A gene, and rs16861329 (C>T) near the ST6GAL1 gene. Genotyping was performed using polymerase chain reaction (PCR) followed by Sanger sequencing of PCR amplicons. The relationship between T2DM and various anthropometric traits was examined in a cohort of 100 North Indian participants, comprising 60 individuals with T2DM and 40 ethnically matched healthy controls. Enrolment was based on inclusion and exclusion criteria, with participants required to provide written informed consent. Diagnostic criteria included glycated haemoglobin (HbA1c) ≥ 6.5% and fasting plasma glucose ≥126 mg/dL.

RESULTS

Significant differences in genotype and allele frequencies were observed for AP3S2-rs2028299 (P <0.001 for both) and ST6GAL1-rs16861329 (P = 0.018 and P = 0.048, respectively) between T2DM patients and controls. The CA genotype of rs2028299 was strongly associated with T2DM incidence (odds ratio [OR] = 12.60; 95% confidence interval [CI]: 3.93-39.93), while the CT genotype of rs16861329 also showed significant association (OR = 2.72; 95% CI: 1.18-6.27). For the VPS26A-rs1802295 polymorphism, total cholesterol levels were highest in TT carriers (166.74 ± 50.10 mg/dL), followed by CC carriers (165.56 ± 37.28 mg/dL).

CONCLUSION

The AP3S2-rs2028299 CA variant and ST6GAL1-rs16861329 CT variant may serve as potential genetic biomarkers for T2DM development in the North Indian population.