Association of Genetic Variants With Rapid Fibrosis: Progression After Liver Transplantation for Hepatitis C Journal Article


Authors: Layden, J. E.; Tayo, B. O.; Cotler, S. J.; Clark, N. M.; Baraoidan, K.; Friedman, S. L.; Cooper, R. S.
Article Title: Association of Genetic Variants With Rapid Fibrosis: Progression After Liver Transplantation for Hepatitis C
Abstract: BACKGROUND: Recurrence of hepatitis C, the main indication for liver transplantation in the United States, leads to rapid fibrosis progression and worse outcomes compared to other indications. While clinical variables play a role, they are insufficient to explain all inter-patient variability in posttransplant fibrosis progression. Genetic factors associated with hepatitis C virus (HCV) outcomes have been identified, but limited studies have been conducted in the context of HCV-related liver transplantation. Therefore, the purpose of this study was to examine candidate genes related to the immune response and rate of fibrosis in subjects undergoing liver transplantation for HCV. METHODS: One hundred twelve recipients with detailed posttransplant fibrosis and clinical information were genotyped using 25 single nucleotide variants (SNVs), including five SNVs within the IL28B gene region. Associations between SNVs and rapid fibrosis progression were performed controlling for pertinent clinical variables and haplotype analyses for the IL28B gene were completed. RESULTS: Significant multivariable associations were found for rs8099917 (IL28B), rs1991401 (DDX5), rs4969168 (SOC3), and rs7976497 (MLEC). The minor allele was protective against rapid fibrosis progression for the IL28B SNV (G allele), MLEC SNV (T allele), and DDX5 SNV (G allele). For the SOC3 SNV, the minor allele (A) increased the risk for rapid fibrosis progression. Additionally, two recipient haplotype structures for IL28B were significantly associated with rapid fibrosis progression. CONCLUSIONS: These findings indicate that recipient genetic factors play a role in posttransplant HCV-related fibrosis progression. Molecular studies of these pathways may elucidate the pathogenesis of posttransplant fibrosis progression and provide risk prediction markers.
Keywords: Adult; Female; Humans; Middle Aged; Male; Follow-Up Studies; Liver/pathology; Genotype; Alleles; Liver Transplantation; Disease Progression; DNA/genetics; Genetic Variation; Haplotypes; Hepatitis C, Chronic/surgery; Interleukins/genetics/metabolism; Liver Cirrhosis/etiology/genetics/pathology
Journal Title: Transplantation
Volume: 97
Issue: 10
ISSN: 1534-6080; 0041-1337
Publisher: Unknown  
Date Published: 2014
Start Page: 1072
End Page: 1078
Language: ENG
DOI/URL:
Notes: LR: 20150806; GR: P20 AA017067/AA/NIAAA NIH HHS/United States; GR: R01 AA020709/AA/NIAAA NIH HHS/United States; GR: R01 DK037340/DK/NIDDK NIH HHS/United States; GR: R01 DK056621/DK/NIDDK NIH HHS/United States; GR: R01DK56621/DK/NIDDK NIH HHS/United States; JID: 0132144; 0 (IL28B protein, human); 0 (Interleukins); 9007-49-2 (DNA); NIHMS710967; OID: NLM: NIHMS710967; OID: NLM: PMC4524502; ppublish
LUC Authors
  1. Nina Clark
    30 Clark
  2. Bamidele Olusegun Tayo
    83 Tayo
  3. Richard Stanley Cooper
    113 Cooper
  4. Jennifer Layden
    22 Layden
  5. Scott Cotler
    70 Cotler
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