title: Promoter activity of human tissue inhibitor of metalloproteinase 2 gene with novel single nucleotide polymorphisms.
abstract: OBJECTIVE
  The single nucleotide polymorphism (SNP) -418G > C in the TIMP2 gene promoter region has been shown to be associated with in chronic obstructive pulmonary disease (COPD). The purpose of this study was to search for novel single nucleotide polymorphism (SNP) in the TIMP2 promoter region around the -418G > C locus, and to investigate whether any of these SNP, including -418G > C, had an influence on TIMP2 transcription activity.
  
  
  METHODS
  DNA sequencing was performed on a 689 base-pair polymerase chain reaction fragment of the promoter region. The novel SNP were characterized and genotype analysis was performed for COPD and control subjects. A reporter gene assay was performed using the wild-type promoter (-418G/-177C/+34C) and the mutant-type promoter (-418C/-177T/+34A).
  
  
  RESULTS
  Nine novel SNP were identified. The SNP -177C > T and +34C > A were in complete linkage disequilibrium with -418G > C. The other seven SNP were not associated with COPD. No significant difference was detected in the reporter gene assay between the activities of the wild-type and the mutant-type promoters.
  
  
  CONCLUSIONS
  The SNP -418G > C, -177C > T and +34C > A, might not themselves be functional from a transcriptional point of view in the development of COPD, but may be in linkage disequilibrium with other functional polymorphisms.
authors.affiliation: Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Uchida
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: Mie
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Wataru
authors.initials: W
authors.lastname: Saitoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizuka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kiwamoto
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
mesh_terms: D020029:Base Pairing / Q000235:genetics; D016022:Case-Control Studies; D003596:Cytosine; D005787:Gene Frequency / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D005838:Genotype; D006147:Guanine; D006801:Humans; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000235:genetics; D017422:Sequence Analysis, DNA; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; D006147:Guanine; D003596:Cytosine