Tumour necrosis factor alpha (-238 and -308) and beta gene polymorphisms in pulmonary tuberculosis: haplotype analysis with HLA-A, B and DR genes

Setting:Astudyof tumournecrosisfactor aand b (TNFaand b) genepolymorphismandhaplotypeanalysiswith HLA in pulmonary tuberculosis. Objective: To determine whether TNFa (-238 and -308) and TNFb (Nco I polymorphism in intron 2) genes either alone or in combinationwith human leucocyte antigens (HLA) as haplotypes afford susceptibilityor resistance to pulmonary tuberculosis aswell asbacteriological relapse of the disease. Design: Tumour necrosis factor a -238, -308 (TNFa -238, -308) and TNFb (Nco I) gene polymorphismswere carried out in HLA- A,Band DR typed pulmonary tuberculosis patients (n = 210) and120 normalhealthy control subjects. Results: No difference in the genotype frequencies of TNFa-238 and -308 and TNFb was seen between control subjects and pulmonary tuberculosispatients.Of the HLA-TNFhaplotypes analysed, theinfrequent allele (A) of TNFa238 wasin stronglinkage disequilibriumwith HLA-A1 (Pcorrected:Pc = 0.001),B17 (Pco0.0001) and DR7 (Pc = 0.01) in control subjects andwith B17 (Pco0.0001) in pulmonary tuberculosis.The infrequent allele 2 of TNFa-308 and the infrequent allele 2 of TNFb were in strong linkage disequilibriumwith HLA-B21.An increased haplotype frequency of HLA-B17-TNFa-238/A (P = 0.05),B17-TNFa308/2 (P=0.03) andB17-TNFa308/2 (P = 0.01) was observedin bacteriological relapse patients than quiescent patients. Conclusion: The present study suggests that TNFa (-238 and -308) and TNFb gene variants are not associated independently with the susceptibility to pulmonary tuberculosis.However, in combinationwith the HLAgenes/gene products such as HLA-A1, B17,B21and DR7, theTNFaand bgenes ashaplotypes are associatedwith protection against the disease aswellas anincreased susceptibility to bacteriological relapse