Details

Autor(en) / Beteiligte

• AKAHOSHI, Mitsuteru
• ISHIHARA, Mami
• OHNO, Shigeaki
• NAKASHIMA, Hitoshi
• CASANOVA, Jean-Laurent
• HOPKIN, Julian M
• TAMARI, Mayumi
• MAO, Xiao-Quan
• SHIRAKAWA, Taro
• REMUS, Natascha
• UNO, Kazuko
• MIYAKE, Katsuhisa
• HIROTA, Tomomitsu
• NAKASHIMA, Kazuko
• MATSUDA, Akira
• KANDA, Mizuo
• ENOMOTO, Tadao

Titel

Association between IFNA genotype and the risk of sarcoidosis

Ist Teil von

• Human genetics, 2004-04, Vol.114 (5), p.503-509

Ort / Verlag

Heidelberg: Springer

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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, P(c)=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-alpha and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN-alpha significantly increases the risk of sarcoidosis.