Although genetic factors may affect susceptibility to tuberculosis, studies that have assessed variants of the natural resistance-associated macrophage protein 1 gene (NRAMP1) and their association with tuberculosis in humans have yielded conflicting results. It is likely that NRAMP1 polymorphisms may be associated with progression to severe forms of pulmonary tuberculosis rather than with susceptibility to Mycobacterium tuberculosis infection. To test this possibility, we examined NRAMP1 variants at the INT4 and D543N loci, as well as their association with severe forms of pulmonary tuberculosis, in 127 patients with active pulmonary tuberculosis and in 91 ethnically matched, healthy control subjects in areas of China where tuberculosis is endemic. We found that NRAMP1 polymorphisms at these 2 loci were significantly associated with 2 severe forms of pulmonary tuberculosis: sputum smear-positive tuberculosis and cavitary tuberculosis. The NRAMP1 variants were not associated with pulmonary M. tuberculosis infection, when analyses of all patients with tuberculosis and all control subjects were performed. The findings of the present study support the hypothesis that genetic variants of NRAMP1 may have an effect on bacilli growth and on outcomes of pulmonary tuberculosis, but not on susceptibility to M. tuberculosis infection.
The full-length hNdrg2 cDNA-coded 357 amino acids was cloned and expressed in Escherichia coli strain DH5alpha as a 6x His-tagged protein. The purified 6x His-fusion protein was used to immunize mice for preparing monoclonal antibodies (mAb) against N-myc downstream-regulated gene 2 (Ndrg2). A hybridoma secreting a monoclonal antibody against Ndrg2 was obtained and named FMU-Ndrg2.3. Western blot analysis confirmed that this mAb is specific only to Ndrg2 but not to Ndrg1, Ndrg3, and Ndrg4-B. Some tissue distribution features of Ndrg2 proteins, such as thyroid, kidney, testis, prostate, and pancreas islets, were present by immunohistochemistry.
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