Cureus · 2026
Association of Interleukin-4 (rs224320), Interleukin-18 (rs1946518 and rs187238), and Tumor Necrosis Factor Receptor 2 (rs1061622) Gene Polymorphisms With Type 2 Diabetes Mellitus in a Rural South-Western Maharashtra Population.
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Patil Monika S, Mane Priyanka M, Kale Shivani R, Patil Sonika S, Kakade Satish V, Patil Satish
Аннотация
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.
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.