title: Identification of MICA as a susceptibility gene for pulmonary Mycobacterium avium complex infection.
abstract: Host genetic susceptibility to adult pulmonary Mycobacterium avium complex disease remains unknown. To identify genetic loci for the disease, we prepared 3 sets of pooled DNA samples from 300 patients and 300 sex-matched control subjects and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009i-located in the MICA (major histocompatibility complex class I chain-related A) gene, which encodes a ligand of the NKG2D receptor-had the lowest P value in pooled and individual DNA typing. The A6 allele of the microsatellite was significantly associated with female patients (P <. 001), whereas the classical HLA-B and HLA-DRB1 alleles did not show significant association. Functional analysis of allelic expression imbalance revealed that A6-derived messenger RNA was more highly expressed than non-A6-derived messenger RNA in human bronchial epithelial cells. MICA was expressed in bronchiolar epithelium, alveolar macrophages, and granulomatous lesions. These findings suggest that MICA might be one of the immune molecules affecting the pathogenesis of the disease.
authors.affiliation: Department of Respiratory Diseases, University of Tokushima, Graduate School, Tokushima, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Shojima
authors.forename: Goh
authors.initials: G
authors.lastname: Tanaka
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ando
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Emiko
authors.initials: E
authors.lastname: Toyota
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kudo
authors.forename: Akira
authors.initials: A
authors.lastname: Kajiki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagai
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Kurashima
authors.forename: Norihiro
authors.initials: N
authors.lastname: Oketani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Tamiko
authors.initials: T
authors.lastname: Takemura
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Takatomo
authors.initials: T
authors.lastname: Morita
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Sakurada
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
mesh_terms: D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D015270:Mycobacterium avium-intracellulare Infection / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A