Genetic polymorphism in the MMP7 gene correlates with the development of bronchiolitis obliterans syndrome

Abstract

Bronchiolitis obliterans syndrome (BOS) is the manifestation of chronic allograft rejection after lung transplantation and affects about 50% of the lung transplant recipients within 5 years. Airway epithelium is the primary target of injury (allo-dependent and -independent) in the pathogenesis of BOS and therefore mechanisms for epithelial repair are required. Matrix metalloproteinase-7 (MMP-7) expression is induced by injury and is essential for lung repair and re-epithelialisation. MMP-7 might be of importance in the development of BOS.The aim of this study is to evaluate the role of single nucleotide polymorphisms (SNPs) in the MMP7 gene and the development of BOS.DNA from patients who underwent a lung transplantation in the Heart Lung Centre in Utrecht, the Netherlands, in the period from 2001 to 2008, was collected. The controls comprised 425 healthy individuals.Six SNPs (rs1996352, rs12285347, rs17884789, rs10502001, rs11568819, rs17098318) in the MMP7 gene were genotyped. The diagnosis BOS was defined according to the ISHLT guidelines.In total, 110 patients filled in an informed consent and donated blood. Seventeen patients were diagnosed with BOS.The BOS group had a significant higher G allele frequency for rs17098318 (promoter region) compared to the controls (0.97 vs 0.62, p<0.001). The rs17098318 GG genotype frequency in the BOS group was 94% (n=16) vs 41% (n=172) in the healthy controls (p<0.001).Lung transplant recipients with rs17098318 GG might be predisposed to develop BOS. Further research will follow to determine if this SNP has functional consequences for the production of MMP-7.Date: Sunday, September 13, 2009Session Info: Oral Presentation: Bronchiolitis obliterans syndrome after lung transplantation: pathophysiology and treatment options