Association of the SLC11A1 Gene Polymorphisms With Susceptibility to Mycobacterium Infections in a Japanese Population

Abstract Genetic factors may be involved in the susceptibility to mycobacterium infection. We studied the association of polymorphisms in the candidate gene, SLC11A1 (solute carrier family 11 member 1; formerly NRAMP1), which controls immune reactions to intracellular pathogens, with susceptibility to active Mycobacterium tuberculosis and nontuberculous mycobacterium infections in a Japanese population, who was admitted to a local hospital in the Kanagawa prefecture. A case-control study was performed by comparing the frequency of polymorphisms in the SLC11A1 gene in patients with pulmonary tuberculosis (57 cases) or with Mycobacterium avium-intracellulare infection (17 cases) and ethnically matched healthy controls (51 cases). Three SLC11A1 genetic polymorphisms, G/C at intron 4 (496+14G/C), transformation of aspartic acid to asparagine at 543 codon (D543N), and TGTG deletion in 3′ untranslated region (1729+55del4) were examined, using restriction fragment length polymorphism analysis of polymerase chain reaction products. The polymorphism of D543N wasfound closely associated with both pulmonary tuberculosis (P = 0.009) and M. avium-intracellulare infection (P = 0.01). The polymorphism of intron 4 was closely associated only with pulmonary tuberculosis (P = 0.05). The polymorphisms in SLC11A1 may partly explain the susceptibility to active M. tuberculosis and M. avium-intracellulare infections without predisposing factors in a Japanese population.