TY - JOUR
T1 - Identification of MICA as a susceptibility gene for pulmonary Mycobacterium avium complex infection
AU - Shojima, Junko
AU - Tanaka, Goh
AU - Keicho, Naoto
AU - Tamiya, Gen
AU - Ando, Satoshi
AU - Oka, Akira
AU - Lnoue, Yoshikazu
AU - Suzuki, Katsuhiro
AU - Sakatani, Mitsunori
AU - Okada, Masaji
AU - Kobayashi, Nobuyuki
AU - Toyota, Emiko
AU - Kudo, Koichiro
AU - Kajiki, Akira
AU - Nagai, Hideaki
AU - Kurashima, Atsuyuki
AU - Oketani, Norihiro
AU - Hayakawa, Hiroshi
AU - Takemura, Tamiko
AU - Nakata, Koh
AU - Ito, Hideyuki
AU - Morita, Takatomo
AU - Matsushita, Lkumi
AU - Hijikata, Minako
AU - Sakurada, Shinsaku
AU - Sasazuki, Takehiko
AU - Lnoko, Hidetoshi
N1 - Funding Information:
Received 20 October 2008; accepted 18 December 2008; electronically published 28 April 2009. Potential conflicts of interest: none reported. Presented in part: 46th Annual Meeting of the Japanese Respiratory Society, Tokyo, 1–3 June 2006 (abstract OP511). Financial support: Ministry of Education, Culture, Sports, Science, and Technology of Japan (grants-in-aid for scientific research on priority areas, 2001–2005); National Hospital Organization of Japan (grant for category network). a J.S. and G.T. contributed equally to this work. Reprints or correspondence: Dr. Naoto Keicho, Dept. of Respiratory Diseases, Research Institute, International Medical Center of Japan, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan (nkeicho-tky@umin.ac.jp).
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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 sexmatched control subjects and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009ilocated 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-DRBl alleles did not show significant association. Functional analysis of allelic expression imbalance revealed that A6derived 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.
AB - 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 sexmatched control subjects and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009ilocated 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-DRBl alleles did not show significant association. Functional analysis of allelic expression imbalance revealed that A6derived 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.
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U2 - 10.1086/598982
DO - 10.1086/598982
M3 - Article
C2 - 19405864
AN - SCOPUS:67650659382
SN - 0022-1899
VL - 199
SP - 1707
EP - 1715
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -
