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TIMP-3 promoter variants and pigeon breeder’s disease

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Pigeon breeder’s disease (PBD) is a granulomatous inflammatory disease of the lung that occurs in people exposed to bird antigens (hypersensitivity pneumonitis). In this and several other diseases, such as idiopathic pulmonary fibrosis (IPF), rheumatoid arthritis, and cancer, there is a change in the balance of proteolysis and antiproteolysis brought about by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). This balance determines the turnover of extracellular matrix. There is evidence that polymorphisms in MMP and TIMP genes may influence susceptibility to disease. Researchers in Mexico and the UK have assessed the role of promoter variants in the TIMP-3 gene because of TIMPs -1, -2, -3, and -4, only TIMP-3 binds strongly to extracellular matrix.

They studied the allele frequency and genotype distribution of two TIMP-3 promoter polymorphisms, –915A>G and –1296T>C, among 622 Mexican adults, 115 with PBD, 90 bird keepers without PBD, 94 with IPF, and 323 healthy controls. Each of the variants occurred in about one in 300 (0.33%) in each of the control and IPF groups and about one in 444 (0.225%) of the PBD group. Carriage of at least one variant allele was 52% protective against PBD. Of four haplotypes at positions –915 and –1296 the *G*C haplotype was 47% protective against PBD. Among subjects in the PBD group the *G*C haplotype did not influence lung function or severity of lung fibrosis but this haplotype was associated with a reduction in the proportion of cells in bronchoalveolar lavage fluid that were lymphocytes.

The two promoter variants in the TIMP-3 gene were associated with reduced risk of PBD possibly because of reduced inflammatory reaction rather than a reduction in fibrosis.