title: Mannose-binding lectin and ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation.
abstract: OBJECTIVE
  The lectin pathway of complement activation is a crucial effector cascade of the innate immune response to pathogens. Cytomegalovirus (CMV) infection occurs frequently in immunocompromised patients after orthotopic liver transplantation (OLT). Single-nucleotide polymorphisms (SNPs) in the lectin pathway genes determine their liver-derived protein level and functional activity. We examined the association between these SNPs and the risk for CMV infection in OLT.
  
  
  METHODS
  OLT patients (n = 295) were genotyped for recipient and donor SNPs in mannose-binding lectin (MBL2), Ficolin-2 (FCN2) and MBL-associated serine protease (MASP2) genes.
  
  
  RESULTS
  Combined analysis of independently associated variant MBL2 [HR 1.65, p<0.02] and wild-type FCN2 [1.85; p<0.02] SNPs in the donor liver showed an increased risk of CMV infection for either and both risk genotypes [HR 2.02 and HR 3.26, respectively, p = 0.004], especially in CMV Donor-/Recipient+ (D-/R+) patients [HR 4.7 and HR 10.0, respectively, p = 0.01]. A genetic donor-recipient mismatch for MBL2 and FCN2 increased the CMV risk independently, also combined [HR 5.35; p<0.001], particularly in CMV D-/R+ patients [HR 16.6; p = 0.009]. Multivariate Cox analysis showed a consistent stepwise increase in CMV infection risk with the gene profile of the donor [up to HR 2.77; p<0.005] and the combined MBL2 and FCN2 donor-recipient mismatch profile [up to HR 4.57; p<0.001], independent from donor-recipient CMV serostatus, also at higher CMV (re)infection cut-off values.
  
  
  CONCLUSIONS
  MBL2 and FCN2 risk alleles of donor liver and recipient constitute independent risk factors for CMV infection after OLT. Patients with these risk genes probably need intensified CMV monitoring and anti-viral therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bert-Jan F
authors.initials: BJ
authors.lastname: de Rooij
authors.forename: Martha T
authors.initials: MT
authors.lastname: van der Beek
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
authors.forename: Ann C T M
authors.initials: AC
authors.lastname: Vossen
authors.forename: W
authors.initials: W
authors.lastname: Rogier Ten Hove
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schaapherder
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
authors.forename: Johan J
authors.initials: JJ
authors.lastname: van der Reijden
authors.forename: Minneke J
authors.initials: MJ
authors.lastname: Coenraad
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.forename: Hein W
authors.initials: HW
authors.lastname: Verspaget
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D037102:Lectins / Q000235:genetics*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D055815:Young Adult; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C445619:MBL2 protein, human; C105296:MASP2 protein, human