Gene expression patterns in livers of Hispanic patients infected with hepatitis C virus

• Published in: Autoimmunity (Chur, Switzerland) Vol. 44; no. 7; pp. 532 - 542
• Main Authors: Hevezi, Peter A., Tom, Edward, Wilson, Keith, Lambert, Peter, Gutierrez-Reyes, Gabriela, Kershenobich, David, Zlotnik, Albert
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.11.2011; Taylor & Francis
• Subjects: Adolescent; Adult; Aged; Antiviral Agents - administration & dosage; Biopsy; Female; gene expression; Gene Expression Regulation, Viral; Hepacivirus - isolation & purification; hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - ethnology; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - metabolism; Hispanic Americans - genetics; Humans; Interferon-alpha - administration & dosage; Male; Mexico; Microarrays; Middle Aged; Oligonucleotide Array Sequence Analysis; Polyethylene Glycols - administration & dosage; Prospective Studies; Recombinant Proteins - administration & dosage; Reverse Transcriptase Polymerase Chain Reaction; Ribavirin - administration & dosage; Ribavirin - pharmacology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Young Adult
• ISSN: 0891-6934; 1607-842X
• DOI: 10.3109/08916934.2011.592881

We report a gene expression study aimed at the identification of genes differentially expressed in the livers of Hispanic patients infected with hepatitis C virus (HCV). Six uninfected controls were compared with 14 HCV(+) patients in which the liver biopsies were obtained at the time of diagnosis. Among the latter, five patients were also analyzed 4 weeks after the onset of standard anti-HCV therapy (pegylated interferon-α + ribavirin). We identified many genes up- or down-regulated by the infection with HCV in the human livers. When these genes were subjected to pathway analysis, several prominent pathways were revealed including many interferon (IFN)-inducible pathways as well as immune cell trafficking, inflammation, anti-microbial responses, and even cancer. We detected expression of many genes that have previously been associated with HCV infection, as well as several novel genes including CD47. The genes induced by HCV infection showed large expression changes, whereas the genes induced by the IFN-α combination therapy were relatively few (including MX2, ORMDL3, GPAM, KOPX18, TMEM56, and HBP1) and they reflected relatively small expression changes. This is the first study to identify changes in gene expression in livers of HCV(+) Hispanic patients and the first to identify genes induced by anti-HCV combination therapy in the human liver.