Identification of MICA as a susceptibility gene for pulmonary Mycobacterium avium complex infection.
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.
Shojima
Junko
J
Department of Respiratory Diseases, University of Tokushima, Graduate School, Tokushima, Japan.
Tanaka
Goh
G
Keicho
Naoto
N
Tamiya
Gen
G
Ando
Satoshi
S
Oka
Akira
A
Inoue
Yoshikazu
Y
Suzuki
Katsuhiro
K
Sakatani
Mitsunori
M
Okada
Masaji
M
Kobayashi
Nobuyuki
N
Toyota
Emiko
E
Kudo
Koichiro
K
Kajiki
Akira
A
Nagai
Hideaki
H
Kurashima
Atsuyuki
A
Oketani
Norihiro
N
Hayakawa
Hiroshi
H
Takemura
Tamiko
T
Nakata
Koh
K
Ito
Hideyuki
H
Morita
Takatomo
T
Matsushita
Ikumi
I
Hijikata
Minako
M
Sakurada
Shinsaku
S
Sasazuki
Takehiko
T
Inoko
Hidetoshi
H
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
D005819:Genetic Markers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A