title: A functional polymorphism in MMP-9 is associated with childhood atopic asthma.
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.
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakashima
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Obara
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.forename: Shigemi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Ebisawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
mesh_terms: D024506:5' Flanking Region; D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020545:Respiratory Mucosa / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008156:Luciferases; D020780:Matrix Metalloproteinase 9