02015nas a2200229   4500000000100000008004100001260001300042653001200055653003800067653001100105653002100116653001800137653002900155100001400184245008100198856006200279300000900341490000600350050001700356520139800373022001401771       2003                            d  c2003 Jan10aAnimals10aGenetic Predisposition to Disease10aHumans10aImmunity, Innate10aMycobacterium10aMycobacterium Infections1 aBellamy R00aSusceptibility to mycobacterial infections: the importance of host genetics.  uhttp://www.nature.com/gene/journal/v4/n1/pdf/6363915a.pdf  a4-110 v4  aBELLAMY 20033 a<p>There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgammaR) ligand binding chain, IFNgammaR signal transduction chain, IFNgamma signal transduction and activation of transcription-1, interleukin 12 receptor beta1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.</p>  a1466-4879