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Polymorphisms of the NRAMP1 gene: Distribution and susceptibility to the development of pulmonary tuberculosis in the Greek population

Marios K. Stagas, Georgios S. Papaetis, Dora Orphanidou, Charalambos Kostopoulos, Stavroula Syriou, Martin Reczko, Nikolaos Drakoulis

Med Sci Monit 2011; 17(1): PH1-6

DOI: 10.12659/MSM.881312


Background:    Ample evidence suggests that host genetic factors affect human susceptibility to tuberculosis. The natural resistance–associated macrophage protein 1 (NRAMP1) gene seems to play a role in the pathophysiology of a number of intracellular infections, including mycobacteria. A case-control study was conducted in the Greek population to determine whether NRAMP1 polymorphisms affect the susceptibility to development of overt pulmonary tuberculosis.
    Material/Methods:    NRAMP1 polymorphisms (3’UTR, D543N, INT4) were evaluated among 142 patients with culture-positive pulmonary tuberculosis and 144 ethnically matched healthy controls having latent M. tuberculosis infection. Patients with human immunodeficiency virus infection were excluded.
    Results:    Out of the 3 NRAMP1 polymorphisms, a trend of increased incidence of INT4 polymorphism was found in the patients’ group compared to the control group. A lack of association was observed between the 2 groups as far as the other 2 polymorphisms (D543N, 3’UTR) are concerned. INT4-CC homozygotes were found to have a higher risk to develop pulmonary tuberculosis compared to GG homozygotes (p=0.022). An increased incidence G/TGTG/C genotype combination was found in the patients’ group as compared to controls. G/TGTG/C genotype combination was associated with a 36% higher risk of developing pulmonary tuberculosis (p=0.004) compared to the baseline expression of G/TGTG/G combination.
    Conclusions:    INT4-NRAMP1 polymorphism may have a role in the development of culture-positive pulmonary tuberculosis after an initial M. tuberculosis latent infection. The possible role of INT4-NRAMP1 polymorphism in the development of active pulmonary tuberculosis needs further investigation.

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