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A polymorphism in the inducible nitric oxide synthase gene is associated with tuberculosis

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Gómez, Luis Miguel
Anaya, Juan-Manuel
Vilchez, José Ramón
Cadena, Jose
Hinojosa, Rosa
Vélez, Luciano
Lopez-Nevot, Miguel Angel
Martín, Javier

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2007

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Abstract
iNOS or NOS2 is a molecule that plays a key role in the immunological control of a broad spectrum of infectious agents. Investigation is hampered by difficulty in estimating in vivo production of nitric oxide (NO), but genetic studies provide a potential means of examining the relation between NO production and disease outcome. To better characterize the host genetic factors determining the susceptibility to TB, we evaluated the influence of two polymorphisms in the NOS2A gene on the risk of developing pulmonary TB in a Northwestern Colombian population, which is a moderately-high endemic area. One hundred and fourteen patients with TB and negative for human immunodeficiency virus, plus 304 healthy controls were examined for NOS2A CCTTT and TAAA polymorphisms. A total of 160 healthy controls mentioned before, underwent tuberculin skin test (TST). Analysis disclosed significant differences between patients and controls with NOS2A CCTTT polymorphism (P=0.0001, Pc=0.001, OR=0.4, and 95%CI=0.3-0.7) independent of TST status. When the NOS2A alleles were stratified into short (8-11) and long (12-16) repeats, significant differences with short repeats were observed between TB patients and all controls (P=0.005, OR=0.63, 95%CI=0.46-0.86). No individual association with NOS2A TAAA was detected. These results indicate that a polymorphism in the NOS2A gene influences the susceptibility to TB and suggest a role for NOS2A in the pathogenesis of mycobacterial infection. © 2007 Elsevier Ltd. All rights reserved.
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Amino acid , pulmonary , Inducible nitric oxide synthase , Tuberculin , Adult , Allele , Article , Controlled study , Endemic disease , Female , Gene location , Genetic association , Genetic polymorphism , Genetic risk , Genetic susceptibility , Genetic trait , Human , Immunopathogenesis , Infection risk , Long terminal repeat , Lung tuberculosis , Major clinical study , Male , Priority journal , Sample size , Short tandem repeat , Skin test , Adult , Colombia , Female , Gene frequency , Genetic predisposition to disease , Humans , Male , Middle aged , Nitric oxide synthase type ii , Seroepidemiologic studies , Tandem repeat sequences , Tuberculosis , Genetics , Nitric oxide synthases , Tuberculosis
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