Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation

Liver Int. 2011 Sep;31(8):1110-7. doi: 10.1111/j.1478-3231.2011.02459.x. Epub 2011 Feb 1.

Abstract

Background: Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT.

Aim: To evaluate the relationship between MMP-2 and MMP-9 gene polymorphisms and NAS.

Methods: MMP-2 (-1306 C/T) and MMP-9 (-1562 C/T) gene promoter polymorphisms were analysed in 314 recipient-donor combinations. Serum levels of these MMPs were determined in subgroups of patients as well. NAS were identified with various radiological imaging studies performed within 4 years after OLT and defined as any stricture, dilation or irregularity of the intra- or extrahepatic bile ducts of the liver graft followed by an intervention, after exclusion of hepatic artery thrombosis and anastomotic strictures.

Results: The average incidence of NAS was 15%. The major clinical risk factor for the development of NAS was PSC in the recipient. The presence of the MMP-2 CT genotype in donor and/or recipient was associated with a significantly higher incidence of NAS, up to 29% when both donor and recipient had the MMP-2 CT genotype (P=0.003). In the multivariate analyses, pre-OLT PSC (hazard ratio 2.1, P=0.02) and MMP-2 CT genotype (hazard ratio 3.5, P=0.003) were found to be independent risk factors for the development of NAS after OLT. No obvious association was found between NAS and the MMP-9 genotype and serum levels of the MMPs.

Conclusion: MMP-2 CT genotype of donor and recipient is an independent risk factor, in addition to PSC, for the development of NAS after OLT.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chi-Square Distribution
  • Cholangitis, Sclerosing / complications
  • Cholangitis, Sclerosing / surgery
  • Cholestasis / diagnostic imaging
  • Cholestasis / enzymology
  • Cholestasis / genetics*
  • Constriction, Pathologic
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Liver Transplantation / adverse effects*
  • Logistic Models
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Netherlands
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Proportional Hazards Models
  • Radiography
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9