Defense Date

2007

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology

First Advisor

Dr. Valeria R. Mas

Abstract

Hepatitis C Virus (HCV) infection represents a worldwide pandemic and is currently the leading cause of cirrhosis and liver transplantation. After transplantation recurrence is almost universal with 96% of patients testing positive for viral RNA and exhibiting histological evidence of infection within the first year. Type I interferons (IFN) and interferon inducible genes are responsible for the innate antiviral state and single nucleotide polymorphisms (SNPs) within these genes may affect the patients ability to respond post-transplantation. We hypothesize the elucidation of associations between SNPs in Type-I Interferon and Interferon inducible genes and HCV recurrence post-liver transplantation might help to identify HCV patients with different prognosis and improve liver transplant recipient selection. 100 HCV positive patients were genotyped using Allelic Discrimination on an ABI Prism 7700 sequence detector (Applied Biosystems) for SNPs in IFNB1, OAS-1, and ISG-15 to establish a relationship between SNPs and clinical complications post-transplantation. Quantitative real-time polymerase chain reaction (QPCR) was also run to determine the relationship between SNPs or disease state and the level of RNA expression. Results were collected and analyzed using Fishers exact test, Kaplan-Meir method, and the log-rank test. Results obtained indicated that SNPs in OAS-1 are associated with HCV recurrence within 12 months post-orthotopic liver transplantation (OLT) and OAS-1 SNP genotypes were significantly associated with the development of fibrosis within the first year. Additionally we observed an association between the SNP genotypes of OAS-1 and ISG-15 and CMV infection post-OLT. A significant distribution of ISG-15 genotypes was also found to correlate with acute rejection. These findings might help identify patients at high risk of developing complications within the first year.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

Included in

Physiology Commons

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