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- Title
Association Study of Matrix Metalloproteinase-12 Gene Polymorphisms and Asthma in a Japanese Population.
- Authors
Yamaide, Fumiya; Undarmaa, Siizkhuu; Mashimo, Yoichi; Shimojo, Naoki; arima, Takayasu; Morita, Yoshinori; Hirota, Tomomitsu; Fujita, Kimie; Miyatake, akihiko; Doi, Satoru; Sato, Kazuki; Suzuki, Shuichi; Nishimuta, Toshiyuki; Watanabe, Hiroko; Hoshioka, akira; Tomiita, Minako; Yamaide, akiko; Watanabe, Misa; Okamoto, Yoshitaka; Kohno, Yoichi
- Abstract
Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nu-deotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population. Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagen-esis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. Results: N357S showed a p val-ue<0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00-2.56, p = 0.047; OR 1.40,95% CI 1.04-1.89, p = 0.028, respectively]. This risk variant is associ-ated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-ß. Conclusions: Our results suggest that MMPT2 confers susceptibility to asthma and is associat-ed with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate at-traction of leukocytes to the inflamed tissue.
- Subjects
MATRIX metalloproteinases; ASTHMA; JAPANESE people; SINGLE nucleotide polymorphisms; MUTAGENESIS; DISEASES
- Publication
International Archives of Allergy & Immunology, 2013, Vol 160, Issue 3, p287
- ISSN
1018-2438
- Publication type
Article
- DOI
10.1159/000341672