title: Association of SLC11A1 (NRAMP1) polymorphisms with pulmonary Mycobacterium avium complex infection.
abstract: Although genetic variants in SLC11A1 (NRAMP1) have been associated with mycobacterial diseases, these findings have not been extensively validated in pulmonary Mycobacterium avium complex (MAC) infection. This study investigated the genomic structure of SLC11A1 and its association with MAC infection. Nineteen polymorphic loci were genotyped in European descendents and the Japanese population. Linkage disequilibrium (LD) structures and frequencies of major haplotypes differed between these 2 populations. Tag single nucleotide polymorphisms (SNPs) were chosen from the data set, and 6 polymorphic sites were genotyped in 122 pulmonary MAC cases and 211 controls from Japan. We observed that the T allele of rs2279014 in the 3' untranslated region was associated with protection from MAC disease when comparing allele frequencies with an odds ratio of 0.582 (95% confidence interval 0.379-0.894, p = 0.013). The frequencies of haplotypes constructed with the above 6 variants did not differ between cases and controls. Allele-specific expression imbalance of SLC11A1 mRNA was evaluated in peripheral blood cells from heterozygous individuals, but no difference was observed among haplotypes. Although the significance was modest, rs2279014 is in strong LD with nearby SNPs and further studies are required for conclusive validation.
authors.affiliation: Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Bishwa Raj
authors.initials: BR
authors.lastname: Sapkota
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Goh
authors.initials: G
authors.lastname: Tanaka
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ieki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Emiko
authors.initials: E
authors.lastname: Toyota
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagai
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Kurashima
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D016172:DNA Fingerprinting; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000502:physiology*; D015270:Mycobacterium avium-intracellulare Infection / Q000235:genetics* / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1