title: MMP14 gene polymorphisms in chronic obstructive pulmonary disease.
abstract: Proteinase/antiproteinase imbalance is a widely accepted theory for the pathogenesis of COPD. Among various proteinases, matrix metalloproteinases (MMPs) digest extracellular matrix of the lung and play significant roles in the development of COPD. Polymorphisms of an MMP that upregulate its activity may result in the degradation of the lung matrix. A case-control study was performed to investigate the association of polymorphisms of the MMP14 gene with COPD. Japanese subjects (96 COPD patients and 61 controls) and Egyptian subjects (106 COPD patients and 72 controls) were recruited. Each subject was genotyped for seven single nucleotide polymorphisms (SNPs) of the MMP14 gene; -165 G/T and -72 G/A in the promoter region, +221 C/T in exon 1, +6727 C/G and +6767 G/A in exon 5, +7096 T/C in exon 6, and +8153 G/A in exon 8. The distributions of the genotype frequencies of these SNPs were not significantly different between the COPD patients and the controls in either ethnic group after correction of multiple comparisons. In the haplotype analysis, however, the haplotype -165 T : +221 T : +6727 C : +7096 C had a significantly higher frequency in the Egyptian COPD group than the control group (pcorr = 0.0063). The haplotype of the MMP14 gene, -165 T : +221 T : +6727 C : +7096 C, might be involved in the pathogenesis of COPD.
authors.affiliation: Department of Pulmonary Medicine, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences and University Hospital, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Saitoh
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nomura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kai
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizuka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kiwamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Hosam H
authors.initials: HH
authors.lastname: Massoud
authors.forename: Hosny M
authors.initials: HM
authors.lastname: Massoud
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Hassanein
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
mesh_terms: D000368:Aged; D000483:Alleles; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D012129:Respiratory Function Tests
chemical_list: D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated