title: Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation.
abstract: OBJECTIVE
  IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed at evaluating the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation.
  
  
  METHODS
  In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total of 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed.
  
  
  RESULTS
  IL28B [rs12979860, non-CC (vs. CC) and rs8099917, non-TT (vs. TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs. non-TT) and DDX58 rs10813831 non-GG (vs. GG) were associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p <0.001, vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race, and donor risk index.
  
  
  CONCLUSIONS
  IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.
authors: University of Colorado Denver, Division of Gastroenterology and Hepatology, Aurora, CO 80045, United States. Scott.Biggins@ucdenver.edu
authors: Scott W
authors: SW
authors: Biggins
authors: James
authors: J
authors: Trotter
authors: Jane
authors: J
authors: Gralla
authors: James R
authors: JR
authors: Burton
authors: Kiran M
authors: KM
authors: Bambha
authors: Jennifer
authors: J
authors: Dodge
authors: Megan
authors: M
authors: Brocato
authors: Linling
authors: L
authors: Cheng
authors: Matt
authors: M
authors: McQueen
authors: Lisa
authors: L
authors: Forman
authors: Michael
authors: M
authors: Chang
authors: Igal
authors: I
authors: Kam
authors: Gregory
authors: G
authors: Everson
authors: Richard A
authors: RA
authors: Spritz
authors: Goran
authors: G
authors: Klintmalm
authors: Hugo R
authors: HR
authors: Rosen
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006526:Hepatitis C / Q000453:epidemiology / Q000601:surgery*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011971:Receptors, Immunologic; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index; D014019:Tissue Donors; D014180:Transplantation; D000095022:Interferon Lambda
chemical_list: D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D007372:Interferons; D007378:Interleukins; D011971:Receptors, Immunologic; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C452820:RIGI protein, human