TY - JOUR
T1 - Association between IFNA genotype and the risk of sarcoidosis
AU - Akahoshi, Mitsuteru
AU - Ishihara, Mami
AU - Remus, Natascha
AU - Uno, Kazuko
AU - Miyake, Katsuhisa
AU - Hirota, Tomomitsu
AU - Nakashima, Kazuko
AU - Matsuda, Akira
AU - Kanda, Mizuo
AU - Enomoto, Tadao
AU - Ohno, Shigeaki
AU - Nakashima, Hitoshi
AU - Casanova, Jean Laurent
AU - Hopkin, Julian M.
AU - Tamari, Mayumi
AU - Mao, Xiao Quan
AU - Shirakawa, Taro
N1 - Funding Information:
Acknowledgements We thank Ms. Yuko Furukawa for her skillful technical assistance. This work was supported by a Wellcome Trust International Collaborative Grant and by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labour, and Welfare.
PY - 2004/4
Y1 - 2004/4
N2 - Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process (IFNA17, IFNB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, ETA-1, and NRAMP1) in an association-based study of 102 Japanese patients with sarcoidosis, 114 with tuberculosis, and 110 control subjects. After correction for multiple testing, an IFNA17 polymorphism (551T→G) was found to be associated with susceptibility to sarcoidosis (odds ratio 3.27 [95% CI: 1.44-7.46], P=0.004, Pc=0.04), but not to tuberculosis. We observed no significant associations with the other polymorphisms of the Th1-related genes. We further typed another IFNA polymorphism (IFNA10 60T→A) and confirmed two major haplotypes of the IFNA gene, viz., allele 1: IFNA10 [60T]-IFNA17 [551T] and allele 2: IFNA10 [60A]-IFNA17 [551G], in the Japanese population. In healthy subjects, IFNA allele 2, which is over-represented in patients with sarcoidosis, was significantly associated with increased IFN-α and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN-α significantly increases the risk of sarcoidosis.
AB - Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process (IFNA17, IFNB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, ETA-1, and NRAMP1) in an association-based study of 102 Japanese patients with sarcoidosis, 114 with tuberculosis, and 110 control subjects. After correction for multiple testing, an IFNA17 polymorphism (551T→G) was found to be associated with susceptibility to sarcoidosis (odds ratio 3.27 [95% CI: 1.44-7.46], P=0.004, Pc=0.04), but not to tuberculosis. We observed no significant associations with the other polymorphisms of the Th1-related genes. We further typed another IFNA polymorphism (IFNA10 60T→A) and confirmed two major haplotypes of the IFNA gene, viz., allele 1: IFNA10 [60T]-IFNA17 [551T] and allele 2: IFNA10 [60A]-IFNA17 [551G], in the Japanese population. In healthy subjects, IFNA allele 2, which is over-represented in patients with sarcoidosis, was significantly associated with increased IFN-α and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN-α significantly increases the risk of sarcoidosis.
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U2 - 10.1007/s00439-004-1099-5
DO - 10.1007/s00439-004-1099-5
M3 - Article
C2 - 15004750
AN - SCOPUS:2542477031
SN - 0340-6717
VL - 114
SP - 503
EP - 509
JO - Human Genetics
JF - Human Genetics
IS - 5
ER -
