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018 COMPARISON OF HEPATIC GENE EXPRESSION IN CAUCASIAN AND AFRICAN AMERICAN PATIENTS WITH HEPATITIS C N Anand1, AK Sherker2, I Borozan3, L Chen3, EJ Heathcote4, AM Edwards3, I McGilvray BACKGROUND: It has been estimated that 2.2% of the world's population is infected with Hepatitis C (HCV). African Americans (AA) make up 12% of the American population (75% Caucasian), but represent ~22% of that continent's cases of chronic HCV infection. AA patients with chronic HCV have a lower rate of sustained virological response to treatment with PEG-IFN and ribavirin than do white patients that is not explained by genotype.
1Department of Medicine, University of Toronto, Toronto, Ontario; 2Washington Hospital Center, Washington DC, USA; 3Banting and Best Department of Medical Research; 4Department of Surgery, University of Toronto, Toronto, Ontario
AIM: To investigate the molecular basis for the lower treatment response in AA versus Caucasian HCV patients using gene expression profiling.
METHODS: Expression profiling was performed on percutaneous needle liver biopsies collected from HCV treatment naïve patients. Gene expression levels were compared among eight matched Caucasian and AA patients. All patients were Genotype 1. Patients were matched for (1) age <= 40 or over 40, (2) viral load <= 2,000,000 copies/ml (Low) or >2,000,000 copies/ml (High) (3) Gender (4) Fibrosis, scored as low (F1, F2) or high (F3, F4), and (5) Activity scored as 1 or 2. A meta-analysis technique was used to combine the data. All diseased liver tissue was compared to normal, uninfected controls.
RESULTS: Taking into account cross batch array variability, there was no difference in the gene expression between Caucasian and AA patients. Compared to uninfected liver, both populations had upregulated expression of a number of interferon stimulated genes, such as ISG15, IFIT, OAS2, OAS3 and MX1 as well as a number of immunomodulatory genes, such as B2M and PP2A.
CONCLUSION: Previous work from our laboratory has shown that gene expression in particular an 8 gene subset "signature" comprised of some of the genes found to be up regulated in both Caucasian and AA liver biopsy samples, predicts response to treatment (Chen et al, Gastroenterology 2005). However, we could not find a clear molecular reason for a difference in antiviral response between AA and Caucasians. We found similarities in gene expression profiles across these two different races. Our results now require the we examine the common individual genes for polymorphisms that might underlie the differences in response to treatment.