Background: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory-metabolic disorder in which cytokine-mediated pathways play a crucial role in insulin resistance and β-cell dysfunction. Genetic polymorphisms in inflammatory cytokine genes such as interleukin-4 (IL-4) (rs224320), interleukin-18 (IL-18) (rs1946518 and rs187238), and tumor necrosis factor receptor 2 (TNFR2) (rs1061622) may influence individual risk of T2DM; however, region-specific data from south-western rural Maharashtra, India, remain limited. Objectives: The primary objective was to compare the genotype distributions of selected IL-4 (rs224320), IL-18 (rs1946518 and rs187238), and TNFR2 (rs1061622) polymorphisms between T2DM cases and non-diabetic controls, and to estimate their associations with T2DM after adjustment for relevant demographic and behavioral covariates. Methods: A hospital-based matched case-control study was conducted among 520 participants comprising 260 T2DM patients and 260 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood, and genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype distributions were analyzed using chi-square tests, and binary logistic regression was used to estimate odds ratios (ORs), adjusted odds ratios (AORs), and 95% confidence intervals. A p-value <0.05 was considered statistically significant. Results: Genotype distributions of IL-4 (rs224320), IL-18 (rs1946518, rs187238), and TNFR2 (rs1061622) single-nucleotide polymorphisms (SNPs) differed significantly between cases and controls (p < 0.001). The IL-4 (rs224320) heterozygous genotype was associated with increased T2DM risk (AOR = 2.13, 95% CI: 1.18-3.86; p = 0.012). IL-18 (rs1946518) showed no significant association after adjustment. IL-18 (rs187238) demonstrated significant protective associations for both heterozygous (AOR = 0.19, 95% CI: 0.08-0.43) and variant genotypes (AOR = 0.21, 95% CI: 0.10-0.46; p < 0.001). TNFR2 (rs1061622) showed the strongest associations with increased T2DM risk for both heterozygous (AOR = 6.36, 95% CI: 2.80-14.47) and variant genotypes (AOR = 7.52, 95% CI: 3.48-16.28; p < 0.001). All key associations remained significant after Bonferroni correction, confirming robust genetic associations with T2DM risk. Conclusion: The findings indicate that IL-4 (rs224320) heterozygosity and TNFR2 (rs1061622) genotypes are independently associated with increased T2DM risk, whereas IL-18 (rs187238) genotypes show a protective effect. Associations with IL-18 (rs1946518) were not significant after adjustment. These cytokine gene polymorphisms may contribute to disease risk and require further validation in larger and more diverse populations.
Patil et al. (Mon,) studied this question.
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