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Vol. 160, No. 3, 2013
Issue release date: February 2013
Section title: Original Paper
Int Arch Allergy Immunol 2013;160:287–296
(DOI:10.1159/000341672)

Association Study of Matrix Metalloproteinase-12 Gene Polymorphisms and Asthma in a Japanese Population

Yamaide F.a, b · Undarmaa S.a · Mashimo Y.a · Shimojo N.b · Arima T.b · Morita Y.b · Hirota T.c · Fujita K.d · Miyatake A.e · Doi S.f · Sato K.g · Suzuki S.g · Nishimuta T.g · Watanabe H.g · Hoshioka A.h · Tomiita M.h · Yamaide A.h · Watanabe M.i · Okamoto Y.j · Kohno Y.b · Tamari M.c · Hata A.a · Suzuki Y.a
Departments of aPublic Health and bPediatrics, Graduate School of Medicine, Chiba University, Chiba, cLaboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Yokohama, dSchool of Human Nursing, The University of Shiga Prefecture, Shiga, eMiyatake Asthma Clinic, and fOsaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, gDepartment of Pediatrics, National Shimoshizu Hospital, Yotsukaido, hDepartment of Allergy and Rheumatology, Chiba Children’s Hospital, Chiba, iFirst Department of Pediatrics, Toho University Omori Medical Center, Tokyo, and jDepartment of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/6/2012
Accepted: 7/6/2012
Published online: 10/17/2012
Issue release date: February 2013

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 6

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

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-nucleotide 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 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. Results: 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. Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.

© 2012 S. Karger AG, Basel


  

Author Contacts

Correspondence to: Dr. Yoichi Suzuki
Department of Public Health, Chiba University Graduate School of Medicine
1-8-1 Inohana, Chuo-ku
Chiba 260-8670 (Japan)
Tel. +81 43 226 2068, E-Mail ysuzuki@faculty.chiba-u.jp

  

Article Information

Received: March 6, 2012
Accepted after revision: July 6, 2012
Published online: October 17, 2012
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 6, Number of References : 35

  

Publication Details

International Archives of Allergy and Immunology

Vol. 160, No. 3, Year 2013 (Cover Date: February 2013)

Journal Editor: Valenta R. (Vienna)
ISSN: 1018-2438 (Print), eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/6/2012
Accepted: 7/6/2012
Published online: 10/17/2012
Issue release date: February 2013

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 6

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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