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      Sexual Inequality in Tuberculosis

      1 , 2 , * , 3

      PLoS Medicine

      Public Library of Science

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          Abstract

          Olivier Neyrolles and Lluis Quintana-Murci review the evidence on why tuberulosis notification is twice as high in men as in women in most countries.

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          Most cited references 31

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          Sex differences in autoimmune disease.

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            Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study.

            Susceptibility to disease after infection by Mycobacterium tuberculosis is influenced by environmental and host genetic factors. Vitamin D metabolism leads to activation of macrophages and restricts the intracellular growth of M. tuberculosis. This effect may be influenced by polymorphisms at three sites in the vitamin D receptor (VDR) gene. We investigated the interaction between serum vitamin D (25-hydroxycholecalciferol) concentrations and VDR genotype on susceptibility to tuberculosis. This study was a hospital-based case-control analysis of Asians of Gujarati origin, a mainly vegetarian immigrant population with a high rate of tuberculosis. We typed three VDR polymorphisms (defined by the presence of restriction endonuclease sites for Taq1, Bsm1, and Fok1) in 91 of 126 untreated patients with tuberculosis and 116 healthy contacts who had been sensitised to tuberculosis. Serum 25-hydroxycholecalciferol was recorded in 42 contacts and 103 patients. 25-hydroxycholecalciferol deficiency was associated with active tuberculosis (odds ratio 2.9 [95% CI 1.3-6.5], p=0.008), and undetectable serum 25-hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculosis (9.9 [1.3-76.2], p=0.009). Although there was no significant independent association between VDR genotype and tuberculosis, the combination of genotype TT/Tt and 25-hydroxycholecalciferol deficiency was associated with disease (2.8 [1.2-6.5]) and the presence of genotype ff or undetectable serum 25-hydroxycholecalciferol was strongly associated with disease (5.1 [1.4-18.4]). 25-hydroxycholecalciferol deficiency may contribute to the high occurrence of tuberculosis in this population. Polymorphisms in the VDR gene also contribute to susceptibility when considered in combination with 25-hydroxycholecalciferol deficiency.
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              Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg.

              Natural resistance to infection with intracellular parasites is controlled by a dominant gene on mouse chromosome 1, called Bcg, Lsh, or Ity. Bcg affects the capacity of macrophages to destroy ingested intracellular parasites early during infection. We have assembled a 400 kb bacteriophage and cosmid contig within the genomic interval containing Bcg. A search for transcription units by exon amplification identified six novel genes in this contig. RNA expression studies showed that one of them, designated Nramp, was expressed exclusively in macrophage populations from reticuloendothelial organs and in the macrophage line J774A. Nramp encodes an integral membrane protein that has structural homology with known prokaryotic and eukaryotic transport systems, suggesting a macrophage-specific membrane transport function. Susceptibility to infection (Bcgs) in 13 Bcgr and Bcgs strains tested is associated with a nonconservative Gly-105 to Asp-105 substitution within predicted transmembrane domain 2 of Nramp.
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                Author and article information

                Journal
                PLoS Med
                PLoS
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                December 2009
                December 2009
                22 December 2009
                : 6
                : 12
                Affiliations
                [1 ]Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France
                [2 ]Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France
                [3 ]Institut Pasteur, Human Evolutionary Genetics, CNRS, URA3012, Paris, France
                Author notes

                ICMJE criteria for authorship read and met: ON LQM. Wrote the first draft of the paper: ON LQM. Contributed to the writing of the paper: ON LQM.

                Research in Translation discusses health interventions in the context of translation from basic to clinical research, or from clinical evidence to practice.

                Article
                09-PLME-RIT-2611R2
                10.1371/journal.pmed.1000199
                2788129
                20027210
                Neyrolles, Quintana-Murci. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 6
                Categories
                Research in Translation
                Genetics and Genomics/Genetics of the Immune System
                Immunology/Genetics of the Immune System
                Immunology/Immunity to Infections
                Infectious Diseases
                Infectious Diseases/Bacterial Infections
                Infectious Diseases/Respiratory Infections
                Microbiology/Immunity to Infections
                Physiology/Immunity to Infections
                Respiratory Medicine/Respiratory Infections

                Medicine

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