title: SLC11A1 (formerly NRAMP1) polymorphisms associated with multidrug-resistant tuberculosis.
abstract: The solute carrier family 11 member 1 gene (SLC11A1, formerly known as NRAMP1: natural resistance-associated macrophage protein 1) is one of the host genetic factors reported to affect susceptibility to tuberculosis. The aim of this study was to determine whether SLC11A1 polymorphisms affect the incidence of multidrug-resistant tuberculosis (MDR-TB) and other clinical features of pulmonary tuberculosis. Using polymerase chain reaction and the restriction fragment-length polymorphism analyses, we investigated four previously reported SLC11A1 polymorphisms, variations in 5'(GT)n, INT4, D543N, and 3'UTR in 95 patients with pulmonary tuberculosis including 10 MDR-TB patients. Clinical information, including elapsed time for sputum culture conversion, extent of pulmonary involvement, and presence or absence of cavitary lesions, was based on a review of charts and chest radiographs. For the 10 MDR-TB patients, previous therapy and treatment compliance were also evaluated. Although the number of MDR-TB patients was small, our preliminary study showed that the variations of D543N and 3'UTR are significantly associated with the incidence of MDR-TB (odds ratio [OR]=5.03, 95% confidence interval [CI]=1.24-20.62; P=0.02), longer time to sputum culture conversion (OR=3.86, 95% CI=1.23-12.23; P=0.02), and cavity formation (OR=5.04, 95% CI=1.51-23.13; P=0.02). Three out of the 10 MDR-TB patients with good treatment compliance had at least one genetic variation in SLC11A1. These data suggested that genetic variations in SLC11A1 may affect the incidence of MDR-TB and clinical features of pulmonary tuberculosis. Further studies are needed to confirm this association with increased number of MDR-TB patients.
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tomoji
authors.initials: T
authors.lastname: Abe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Nakashima
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1