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Association between IFNA genotype and the risk of sarcoidosis

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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, 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-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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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.

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Authors and Affiliations

  1. Laboratory for Genetics of Allergic Diseases, SNP Research Center, Institute of Physical and Chemical Research, RIKEN Yokohama Institute, Yokohama, Japan

    Mitsuteru Akahoshi, Tomomitsu Hirota, Akira Matsuda, Mayumi Tamari & Taro Shirakawa

  2. Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan

    Mami Ishihara

  3. Laboratory for Human Genetics of Infectious Diseases, INSERM U550, Necker Medical School, University of Paris Rene Descartes, Paris, France

    Natascha Remus & Jean-Laurent Casanova

  4. Louis Pasteur Center for Medical Research, Kyoto, Japan

    Kazuko Uno

  5. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Mitsuteru Akahoshi, Katsuhisa Miyake & Hitoshi Nakashima

  6. Kanda Hospital, Wakayama, Japan

    Mizuo Kanda

  7. Department of Otolaryngology, Wakayama Medical Center, Japanese Red Cross Society, Wakayama, Japan

    Tadao Enomoto

  8. Department of Ophthalmology, Hokkaido University School of Medicine, Sapporo, Japan

    Akira Matsuda & Shigeaki Ohno

  9. Experimental Medicine Unit, University of Wales at Swansea, Swansea, UK

    Julian M. Hopkin

  10. Department of Health Promotion and Human Behavior, Graduate School of Public Health, Kyoto University, Yoshida-konoe, 606–8501, Kyoto, Japan

    Kazuko Nakashima, Xiao-Quan Mao & Taro Shirakawa

Authors
  1. Mitsuteru Akahoshi
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  2. Mami Ishihara
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  3. Natascha Remus
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  4. Kazuko Uno
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  5. Katsuhisa Miyake
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  7. Kazuko Nakashima
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  8. Akira Matsuda
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  9. Mizuo Kanda
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  10. Tadao Enomoto
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  11. Shigeaki Ohno
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  12. Hitoshi Nakashima
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  13. Jean-Laurent Casanova
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  14. Julian M. Hopkin
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  15. Mayumi Tamari
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  16. Xiao-Quan Mao
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  17. Taro Shirakawa
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Corresponding author

Correspondence to Taro Shirakawa.

Additional information

M. Akahoshi and M. Ishihara contributed equally to this work

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Akahoshi, M., Ishihara, M., Remus, N. et al. Association between IFNA genotype and the risk of sarcoidosis. Hum Genet 114, 503–509 (2004). https://doi.org/10.1007/s00439-004-1099-5

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  • DOI: https://doi.org/10.1007/s00439-004-1099-5

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