Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease

Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of t issue of metalloproteinases-2 (TIMP-2) that downregulate its activity may i ncrease the activities of matrix metalloproteinases and result in the degra dation 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 conforma tional polymorphism analysis followed by sequencing. Two polymorphisms were identified, +853 G/A and -418 G/C nucleotide substit utions. 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 frequen cies 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 varia nt. 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 obstr uctive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibi lity to the disease.