A functional polymorphism in MMP-9 is associated with childhood atopic asthma

Kazuko Nakashima, Tomomitsu Hirota, Kazuhiko Obara, Makiko Shimizu, Satoru Doi, Kimie Fujita, Taro Shirakawa, Tadao Enomoto, Shigemi Yoshihara, Motohiro Ebisawa, Kenji Matsumoto, Hirohisa Saito, Yoichi Suzuki, Yusuke Nakamura, Mayumi Tamari

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Although MMP-9 has been suggested to be important in inflammation and in the connective tissue remodeling associated with asthma, the genetic influences of the polymorphisms of MMP-9 are unclear. To examine whether polymorphisms in MMP-9 are associated with childhood atopic asthma, we identified a total of 17 polymorphisms and conducted an association study with asthma (n = 290) and controls (n = 638). 2127G>T and 5546G>A (R668Q) were significantly associated with the risk of childhood atopic asthma (p = 0.0032 and 0.0016, respectively). In haplotype analysis, we also found a positive association with a haplotype (p = 0.0053). MMP-9 was expressed in cultured human bronchial epithelial cells, and the mRNA expression level was upregulated by dsRNA. Furthermore, the promoter SNP -1590C>T, in strong linkage disequilibrium with 2127G>T, enhanced the transcriptional level of MMP-9. Thus, the MMP-9 gene might be involved in the development of asthma through functional genetic polymorphisms.

Original languageEnglish
Pages (from-to)300-307
Number of pages8
JournalBiochemical and biophysical research communications
Volume344
Issue number1
DOIs
Publication statusPublished - 2006 May 26

Keywords

  • Association study
  • Bronchial asthma
  • Haplotype
  • Linkage disequilibrium
  • MMP-9
  • Polymorphisms
  • Reporter gene assay

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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