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Dept of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
CORRESPONDENCE: Y. Uchida, Dept of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-;1-;1 Tennnoudai Tsukuba, Ibaraki, 305-;8575, Japan. Fax: 81 298533144
Keywords: chronic obstructive pulmonary disease, polymorphism, tissue inhibitors of metalloproteinases
Received: December 6, 2000
Accepted April 3, 2001
Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue inhibitor of metalloproteinases-;2 (TIMP-;2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix.
Polymorphisms of the TIMP-;2 gene were investigated in 88 COPD patients and 40 control subjects. The variations were examined by single-strand conformational polymorphism analysis followed by sequencing.
Two polymorphisms were identified, +853 G/A and –418 G/C nucleotide substitutions. There was a significant deviation in the genotypic frequencies at +853 and the allele frequencies for G were significantly higher in the COPD patient group than in the control group. For locus –418, the allele frequencies for C in the COPD patient group also tended to be higher than those in the control group. The +853 G/A nucleotide substitution was a silent variant. The –418 G/C substitution was located in the consensus sequence for the Sp1 binding site.
These polymorphisms may be associated with the development of chronic obstructive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibility to the disease.
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