Association of The SLC2A4 (GLUT4) Rs5435 Polymorphism with Type 2 Diabetes Mellitus: A Hospital-Based Case–Control Study from Tamil Nadu, South India

Abstract

GLUT4, encoded by SLC2A4, mediates insulin-stimulated glucose disposal into muscle and adipose tissue, and impaired translocation is central to insulin resistance. Evidence linking the synonymous variant rs5435 (Asn130Asn) to type 2 diabetes mellitus is inconsistent across populations, and data from Dravidian populations are sparse. Methods: In an age- and sex-matched case–control study at a tertiary hospital in Chengalpattu, Tamil Nadu (March 2021 to February 2022), 50 adults aged 30–50 years with type 2 diabetes mellitus defined by World Health Organization criteria and without a first-degree family history of diabetes were compared with 50 normoglycaemic controls. rs5435 was genotyped by allele-specific amplification refractory mutation system PCR, with gels read blind to group. Odds ratios with 95% confidence intervals were derived from observed counts, and Hardy–Weinberg equilibrium assessed among controls. Results: Cases and controls were comparable for age (38.74±5.58 versus 38.66±5.77 years, p = 0.944), sex (p = 0.410) and body mass index (p = 0.552). Control genotypes conformed to Hardy–Weinberg equilibrium (p = 0.83). The heterozygous TC genotype was present in 41 of 50 cases (82.0%) and 3 of 50 controls (6.0%), giving an odds ratio of 71.4 (95% CI 18.1–281.5; p<0.001). The minor C allele frequency was 41.0% among cases and 3.0% among controls (odds ratio 22.5, 95% CI 6.7–75.8; p<0.001). No CC homozygote was identified. Conclusions: rs5435 was strongly associated with type 2 diabetes mellitus in this population. The effect size is implausibly large for a common variant and requires confirmation of allele assignment by sequencing, followed by replication in adequately powered cohorts.