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Genetic polymorphisms inMMP7and reduced serum levels associate with the development of bronchiolitis obliterans syndrome after lung transplantation

The Journal of Heart and Lung Transplantation
Publication Date
DOI: 10.1016/j.healun.2010.01.008
  • Bronchiolitis Obliterans Syndrome
  • Matrix Metalloproteinase-7 (Mmp-7)
  • Serum
  • Genetic Polymorphism
  • Lung Transplantation
  • Biology
  • Medicine


Background Pulmonary epithelium is the primary target of injury in the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. Matrix metalloproteinases (MMP)-8 and -9 already have been implicated in the pathogenesis of BOS. MMP-7, which is involved in the repair of the lung epithelium, has not been studied in this respect. We hypothesized that genetic polymorphisms in MMP7 influence its expression and correlate with serum MMP-7 levels and the development of BOS. Methods DNA was collected from 110 lung transplant recipients, including 21 patients with BOS. We genotyped 7 single nucleotide polymorphisms in MMP7 and measured serum MMP-7 levels. The control group comprised 422 healthy individuals. Results BOS pos patients had lower levels of MMP-7 than BOS neg patients (7.87 vs 10.18 ng/ml). Significant differences in genotype and haplotype distribution between the BOS pos and BOS neg patients and controls were found. An increased risk for BOS development was found in patients homozygous for the major alleles of rs17098318, rs11568818, and rs12285347, and for the minor allele rs10502001 (odds ratio, 3.88–5.30). Haplotypes constructed with 3 or 4 risk alleles correlated with lower MMP-7 levels. Conclusions Genetic polymorphisms of MMP7 predispose to the development of BOS. Patients carrying these risk alleles express lower levels of MMP-7, which may contribute to aberrant tissue repair and culminate in the development of BOS.

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