Association between IFNA genotype and the risk of sarcoidosis

Mitsuteru Akahoshi, Mami Ishihara, Natascha Remus, Kazuko Uno, Katsuhisa Miyake, Tomomitsu Hirota, Kazuko Nakashima, Akira Matsuda, Mizuo Kanda, Tadao Enomoto, Shigeaki Ohno, Hitoshi Nakashima, Jean Laurent Casanova, Julian M. Hopkin, Mayumi Tamari, Xiao Quan Mao, Taro Shirakawa

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70 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)503-509
Number of pages7
JournalHuman Genetics
Issue number5
Publication statusPublished - Apr 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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