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16 December 2010

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

Marios K. StagasABCDEFG, Georgios S. PapaetisBDEF, Dora OrphanidouABCDEFG, Charalambos KostopoulosABF, Stavroula SyriouDEF, Martin ReczkoCDE, Nikolaos DrakoulisABDEF

DOI: 10.12659/MSM.881312

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

Abstract

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.

Keywords: Greece - epidemiology, Genotype, Genetic Predisposition to Disease - genetics, DNA Primers - genetics, Cation Transport Proteins - genetics, Case-Control Studies, Incidence, Polymorphism, Genetic - genetics, Tuberculosis - genetics

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