NRAMP1 genetic polymorphisms as a risk factor of tuberculous pleurisy

SETTING: Nramp1 encoded by the NRAMP1 gene influences the phagolysosomal function of alveolar macrophage against Mycobacterium tuberculosis. Genetic polymorphisms of NRAMP1 affect innate host resistance through the defective production and function of Nramp1. OBJECTIVE: To investigate this relationship, the NRAMP1 polymorphisms in patients with tuberculous pleurisy were determined. DESIGN: Pleural biopsy proven 56 patients were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. Three NRAMP1 polymorphisms such as single nucleotide change in intron 4(469+14G/C, INT4), a non-conservative single-base substitution at codon 543(D543N) and TGTG deletion in the 3′ untranslated region (1729+55de14, 3′UTR) were determined. RESULTS: The frequencies of mutant genotypes of INT4 and 3′UTR were significantly high in the pleurisy group (P = 0.01, P = 0.02), but the frequencies of D543N were not significantly different between the two groups. Odds ratios (OR), which are a comparison of the wild with the mutant genotype, were 8.02 (95%CI 2.42∼26.57) for INT4 and 5.73 (95%CI 1.14∼28.92) for 3′UTR which were statistically significant. In the combined analysis of the INT4 and 3′UTR, the ORs were 6.00 (95%CI 1.46∼24.64) for GC/++ genotype and 14.00 (95%CI 1.61∼121.75) for GC/+del when compared with GG/++; these differences were statistically significant. CONCLUSION: The NRAMP1 genetic polymorphisms, especially INT4 and 3′UTR, were closely related to tuberculous pleurisy.