Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma

Michishige Harada, Kazuko Nakashima, Tomomitsu Hirota, Makiko Shimizu, Satoru Doi, Kimie Fujita, Taro Shirakawa, Tadao Enomoto, Mamoru Yoshikawa, Hiroshi Moriyama, Kenji Matsumoto, Hirohisa Saito, Yoichi Suzuki, Yusuke Nakamura, Mayumi Tamari

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73 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (SOCS) 1 is an essential physiologic regulator of the IFN-γ signaling that is crucial to lead appropriate immune responses, and impaired IFN-γ production is considered a hallmark of atopic diseases. Recent study has shown that SOCS1 is also crucial in attenuating type 1 IFN signaling and in limiting the host response to viral infection. Clinical and experimental evidence suggest an important role for respiratory viral infections in the development of asthma. To assess genetic functional variants of SOCS1 related to susceptibility and clinical phenotypes in adult asthma in a Japanese population, we conducted association and haplotype analyses of 462 subjects with adult asthma and 639 control subjects. After screening for polymorphisms, we identified a total of 13 variants and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants were selected for genotyping with regard to the LD pattern, and we found a significant association between an SOCS1 promoter polymorphism -1478CA > del and adult asthma (P = 0.0063). The three-locus haplotype of SOCS1 using these three polymorphisms also showed a positive association with a haplotype T-C-del (-5388T, -3969C, and -1478 del; P = 0.0097). Furthermore, reporter gene analysis revealed that related promoter variant -1478 del enhanced the transcriptional level of SOCS1 in human lung epithelial cells, and induced higher levels of protein expression of SOCS1 and lower phosphorylation of STAT1 stimulated with IFN-β. These findings suggest that the SOCS1 gene might be involved in the development of adult asthma through functional genetic polymorphism.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume36
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

Keywords

  • Association study
  • Bronchial asthma
  • Haplotype
  • Polymorphisms
  • SOCS1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Harada, M., Nakashima, K., Hirota, T., Shimizu, M., Doi, S., Fujita, K., Shirakawa, T., Enomoto, T., Yoshikawa, M., Moriyama, H., Matsumoto, K., Saito, H., Suzuki, Y., Nakamura, Y., & Tamari, M. (2007). Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma. American journal of respiratory cell and molecular biology, 36(4), 491-496. https://doi.org/10.1165/rcmb.2006-0090OC