TAILIEUCHUNG - Footprints of genetic susceptibility to pulmonary tuberculosis: Cytokine gene variants in north Indians

Smear positive pulmonary tuberculosis patients were diagnosed using the following criteria as per the RNTCP guidelines: (i) Two or three smears positive for AFB and (ii) One sputum smear positive for AFB with radiographic abnormalities consistent with active pulmonary tuberculosis. Smear negative pulmonary tuberculosis was diagnosed if three sputum smears were negative for AFB but evidence of radiographic abnormalities of active tuberculosis was present after two weeks of antibiotic treatment for routine bacterial infections of the respiratory tract19. Detection of HIV infection: All patients were given pre-test counselling and tested for anti-HIV antibodies by enzyme-linked immunosorbent assay (ELISA) (Detect HIVMC, Biochem. | Indian J Med Res 135 May 2012 pp 763-770 Footprints of genetic susceptibility to pulmonary tuberculosis Cytokine gene variants in north Indians Abhimanyu Mridula Bose Pankaj Jha Indian Genome Variation Consortium Department of Microbiology Vallabhbhai Patel Chest Institute University of Delhi Genomics Molecular Medicine CSIR-Institute of Genomics Integrative Biology Delhi India Received March 1 2011 Background objectives Tuberculosis is TB responsible for high morbidity and mortality worldwide. Cytokines play a major role in defense against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding the various pro- and anti-inflammatory cytokines have been associated with tuberculosis susceptibility. In this study we examined association of 25 sequence polymorphisms in six candidate cytokine genes namely IFNG TNFB IL4 IL1RA IL1B and IL12 and their related haplotypes with risk of developing pulmonary tuberculosis PTB among north Indians. Methods Pulmonary TB n 110 patients and 215 healthy controls HC from north India were genotyped. Purified multiplex PCR products were subjected to mass spectrometry using Sequenom MassARRAY platform to generate the genotypes in a population-based case-control study. Results Using multiple corrections significant overall risk against PTB was observed at seven loci which included variants in IFNG at rs1861493 and rs1861494 IL1RA at rs4252019 IL4 variant rs2070874 IL12 variants rs3212220 rs2853694 and TNFB variant rs1041981. Analysis of gene structure revealed two haplotype blocks formed by IFNG variants rs1861493 and rs1861494. The TA haplotype was significantly over-represented P in the cases showing a two-fold risk in the current population Odds ratio CI to and TNFB variants at rs2229094 and rs1041981 contributed to two haplotypes which were in strong linkage disequilibrium LD with AT haplotype showing a three-fold risk P Odds ratio 3 CI to of developing PTB in north .

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