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- Title
Association between IFNA genotype and the risk of sarcoidosis.
- Authors
Akahoshi, Mitsuteru; Ishihara, Mami; Remus, Natascha; Uno, Kazuko; Miyake, Katsuhisa; Hirota, Tomomitsu; Nakashima, Kazuko; Matsuda, Akira; Kanda, Mizuo; Enomoto, Tadao; Ohno, Shigeaki; Nakashima, Hitoshi; Casanova, Jean-Laurent; Hopkin, Julian M.; Tamari, Mayumi; Mao, Xiao-Quan; Shirakawa, Taro
- Abstract
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.
- Subjects
JAPAN; SARCOIDOSIS; LYMPHOPROLIFERATIVE disorders; DISEASE risk factors; GENOTYPE-environment interaction; GENETIC polymorphisms; INTERFERONS
- Publication
Human Genetics, 2004, Vol 114, Issue 5, p503
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-004-1099-5