Interleukin-18 cytokine gene polymorphism 137G/C (rs187238) and susceptibility to tuberculosis in north India.

Tuberculosis (TB) regained its position globally as the leading cause of mortality from a single infectious agent after being surpassed by COVID-19 for 3 years consecutively. Host genetic factors, particularly cytokine gene polymorphisms, play a significant role in influencing susceptibility to TB. Interleukin-18 (IL18) is a proinflammatory cytokine involved in immune regulation against Mycobacterium tuberculosis. This study aimed to evaluate the association of IL18 gene polymorphism (rs187238) with susceptibility to TB and its effect on serum IL18 levels in a north Indian population. A case-control study was conducted with 100 newly diagnosed TB patients (pulmonary and extrapulmonary) and 100 age- and gender-matched healthy controls. Serum IL18 levels were measured using sandwich enzyme-linked immunosorbent assay, and the IL18 gene polymorphism at rs187238 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between IL18 polymorphism, TB susceptibility, and serum IL18 levels was statistically evaluated. Mean serum IL18 levels were significantly elevated in TB patients (400.42±149.58 pg/mL) compared to controls (96.05±40.67 pg/mL; p<0.01). The distribution of IL18 genotypes showed that individuals with GC/CC genotypes had a significantly lower risk of developing TB compared to the GG genotype [odds ratio (OR)=0.31; 95% confidence interval (CI)=0.20-0.88; p=0.0167]. Additionally, the C allele conferred a protective effect against TB (OR=0.33; 95% CI=0.22-0.51; p<0.0001). Serum IL18 concentrations varied significantly with genotype, with the highest levels observed in CC genotype carriers in both cases and controls (p<0.01). Thus, our study suggests that IL18 polymorphism at rs187238 significantly influences susceptibility to TB in the north Indian population. The C allele and GC/CC genotypes appear to confer a protective effect, possibly through modulation of IL18 serum levels. IL18 rs187238 polymorphism may serve as an independent predictive marker for TB risk, though larger studies are recommended for validation.