Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis

Polymorphisms in the cytokine genes are known to influence cytokine levels and may be associated with outcome of infections. We investigated the polymorphisms in the cytokine genes namely IFN-gamma (+874 and +5644), IL-2 (-330 and +160), IL-4 (VNTR), IL-6 (-174), IL-10 (-1082 and -819) and IL-12B (+1188) in 188 normal healthy subjects (NHS) and 166 pulmonary tuberculosis patients (PTB) using polymerase chain reaction-based methods. To study the influence of cytokine gene polymorphisms on cytokine levels, phytohaemagglutinin and culture filtrate antigen of Mycobacterium tuberculosis-induced cytokine levels were measured by ELISA from 72-h-old peripheral blood mononuclear cell culture supernatants. Significantly decreased frequency of TT genotype of IL-2 -330 polymorphism (p=0.024, odds ratio (OR) 0.53, 95% CI 0.31-0.92) was observed in patients compared to NHS. The genotype frequencies of other polymorphisms were not different between patients and NHS. IL-12p40 levels were significantly decreased among NHS with AA genotype of IL-12B gene polymorphism compared to NHS with AC genotype (p<0.05). Increased levels of IL-12p40 were observed among patients with CC genotype of IL-12B gene compared to patients with other genotypes (p<0.01). The present study suggests that the TT genotype of IL-2 -330 polymorphism may be associated with the protection to PTB in south India. Further, +1188 polymorphism of IL-12B gene either alone or in combination with closely linked genes may regulate IL-12p40 production and may play a major role on acquired immunity to tuberculosis.