In:
International Archives of Allergy and Immunology, S. Karger AG, Vol. 160, No. 3 ( 2013), p. 287-296
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Matrix metalloproteinase 12 gene 〈 i 〉 (MMP12) 〈 /i 〉 has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of 〈 i 〉 MMP12 〈 /i 〉 are associated with a risk for asthma in a Japanese population. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We tested for an association between SNPs in 〈 i 〉 MMP12 〈 /i 〉 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 mutagenesis 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 N357S showed a p value 〈 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 associated 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-β. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results suggest that 〈 i 〉 MMP12 〈 /i 〉 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. 〈 i 〉 MMP12 〈 /i 〉 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.
Type of Medium:
Online Resource
ISSN:
1018-2438
,
1423-0097
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
1482722-0
Bookmarklink