Promoter activity of human tissue inhibitor of metalloproteinase 2 gene with novel single nucleotide polymorphisms

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. Methodology: 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 incomplete 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.