Polymorphism in the NRAMP1 gene as a risk factor for pulmonary tuberculosis -A case control study

Abstract

Objective: Polymorphism in this gene was determined in pulmonary tuberculosis patients in order to explore this association. Design: We assigned 34 patients with active pulmonary tuberculosis and 30 subjects with latent tuberculosis to the infected group, and 30 healthy household cases to control group. Three polymorphisms were studied, a non-conservative single-base substitution at codon 543(D543N), a single nucleotide change in intron 4(469 14G/C, INT4) and TGTG deletion in the 3 ’ untranslated region (1729 55del4, 3 ’ UTR). Results: No polymorphism was detected in the later two regions. G/A variant was more commonly found in the uninfected group with G/G variant in the infected group. Among the infected group, the G/A variant was significantly associated (44.11%) with active pulmonary tuberculosis. Although homozygous variants (A/A) were also associated (20.58%) with active disease, the prevalence of heterozygous variant found to have a risk eleven folds higher than the later (OR= 11.5). Conclusion: The heterozygous genotype seemed to affect the burden of M. tuberculosis, and in particular the clinical presentation of the disease. Setting: Defective production of protein Nramp1, encoded by gene NRAMP1 disturbs the normal innate host resistance. Keywords: Nramp1, Pulmonary tuberculosis, Polymorphism RFLP.