Genetic polymorphisms in TNF genes and tuberculosis in North Indians

BACKGROUND Pulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by Mycobaterium tuberculosis. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) play important immunoregulatory roles. METHODS To investigate the association of TNF polymorphisms with tuberculosis in the Asian Indians, we genotyped five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene in a clinically well-defined cohort of North-Indian patients with tuberculosis (N = 185) and their regional controls (N = 155). Serum TNF-alpha (sTNF-alpha) levels were measured and correlated with genotypes and haplotypes. RESULTS The comparison of the allele frequencies for the various loci investigated revealed no significant differences between the tuberculosis patients and controls. Also, when the patients were sub-grouped into minimal, moderately advanced and far advanced disease on the basis of chest radiographs, TST and the presence/absence of cavitary lesions, none of the polymorphisms showed a significant association with any of the patient sub-groups. Although a significant difference was observed in the serum TNF-alpha levels in the patients and the controls, none of the investigated polymorphisms were found to affect the sTNF-alpha levels. Interestingly, it was observed that patients with minimal severity were associated with lower log sTNF-alpha levels when compared to the patients with moderately advanced and far advanced severity. However, none of these differences were found to be statistically significant. Furthermore, when haplotypes were analyzed, no significant difference was observed. CONCLUSIONS Thus, our findings exclude the TNF genes as major risk factor for tuberculosis in the North Indians.