title: Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  MMP-2 CT genotype of donor and recipient is an independent risk factor, in addition to PSC, for the development of NAS after OLT.
authors: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
authors: W Rogier
authors: WR
authors: Ten Hove
authors: Kerem S
authors: KS
authors: Korkmaz
authors: Sanna
authors: S
authors: op den Dries
authors: Bert-Jan F
authors: BJ
authors: de Rooij
authors: Bart
authors: B
authors: van Hoek
authors: Robert J
authors: RJ
authors: Porte
authors: Johan J
authors: JJ
authors: van der Reijden
authors: Minneke J
authors: MJ
authors: Coenraad
authors: Jeroen
authors: J
authors: Dubbeld
authors: Daniel W
authors: DW
authors: Hommes
authors: Hein W
authors: HW
authors: Verspaget
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000601:surgery; D002779:Cholestasis / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D003251:Constriction, Pathologic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011859:Radiography; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9