title: Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy.
abstract: OBJECTIVE
  Black American patients are less likely to eradicate hepatitis C virus (HCV) infections during treatment with peginterferon (PEG-IFN) and ribavirin. We hypothesized that racial differences in IFN-stimulated antiviral gene induction during treatment might be responsible.
  
  
  METHODS
  We examined myxovirus resistance-A (MxA), RNA-dependent protein kinase (PKR), 2'-5' oligoadenylate synthetase (2,5-OAS), and adenosine deaminase-1 (ADAR1) gene expression in the peripheral blood mononuclear cells (PBMCs) of 31 black and 11 white HCV genotype 1 patients at baseline and at weeks 4-12 during PEG-IFN alfa-2a combination treatment. The primary study end point was the early virologic response (EVR)-either an undetectable serum HCV-RNA level or a > or =2-log decrease in serum HCV-RNA level at week 12 compared with week 0.
  
  
  RESULTS
  The EVR rate was 67.7% in blacks and 63.6% in whites. Both blacks and whites experienced a significant (200%-500%) increase in 2,5-OAS, MxA, PKR, and ADAR1 expression at treatment weeks 4-12 compared with baseline (P < .01). However, the relationship between IFN-stimulated gene expression and the EVR differed by race. White responders exhibited higher 2,5-OAS and MxA levels at week 4 than white nonresponders (P < .05). IFN-stimulated gene levels did not correlate with EVR in blacks. Black responders had much lower MxA and PKR levels at week 4 than black nonresponders (P < .05). However, black responders maintained increased 2,5-OAS, MxA, and PKR levels from weeks 4-12, whereas the levels decreased to baseline at weeks 8-12 in black nonresponders.
  
  
  CONCLUSIONS
  The mechanisms of resistance to PEG-IFN combination therapy may be different in black and white HCV genotype 1 patients.
authors.affiliation: University of Maryland School of Medicine, USA,
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Luo
authors.forename: William
authors.initials: W
authors.lastname: Cassidy
authors.forename: Lennox
authors.initials: L
authors.lastname: Jeffers
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Christine
authors.initials: C
authors.lastname: Bruno
authors.forename: Charles D
authors.initials: CD
authors.lastname: Howell
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood / Q000235:genetics; D000243:Adenosine Deaminase / Q000097:blood / Q000235:genetics; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044383:Black People / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D044465:White People / Q000235:genetics*; D019892:eIF-2 Kinase / Q000097:blood / Q000235:genetics; D001741:Black or African American
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D019892:eIF-2 Kinase; C115020:OASL protein, human; D015088:2',5'-Oligoadenylate Synthetase; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; C100416:peginterferon alfa-2a