Association of TNF-α polymorphisms rs1800629 (-308G>A) and rs361525 (-238G>A) with type 2 diabetes mellitus in the Punjabi population of Pakistan

Abstract

Background: The TNF-α -promoter polymorphisms rs1800629 (-308G>A) and rs361525 (-238G>A) have been variably associated with type 2 diabetes mellitus (T2DM) risk in different populations. This study evaluated these two polymorphisms in a cohort of Punjabi individuals from Pakistan.

Methods: A case-control study was conducted including 100 clinically diagnosed T2DM patients and 100 healthy controls. Genotyping of TNF-α rs1800629 and rs361525 was performed using allele-specific ARMS-PCR and validated by sequencing. Allele and genotype frequencies were compared between groups, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and Hardy-Weinberg equilibrium was assessed.

Results: The A alleles of rs1800629 and rs361525 were significantly more frequent in T2DM cases compared to controls (3.68% vs. 0.54%, OR = 6.779, p = 0.037 for rs1800629; 5.26% vs. 0.53%, OR = 9.684, p = 0.006 for rs361525). Fasting blood sugar level (FBS) of 150 ± 45 mg/dL was recorded in diabetic subjects. Multivariate and forest plot analyses supported the association of both variants with increased T2DM risk. Control group genotypes conformed to Hardy-Weinberg equilibrium, validating population stability.

Conclusion: In this Punjabi cohort from Pakistan, the A alleles of TNF-α promoter polymorphisms rs1800629 and rs361525 were significantly more frequent in T2DM cases, indicating that these variants increase susceptibility to T2DM in this population.

Keywords: Punjabi population; TNF-α promoter polymorphism; genetic association; rs1800629; rs361525; type 2 diabetes mellitus.