Genomic scale analysis of racial impact on response to IFN-α

Zoltan Pos, Silvia Selleri, Tara L. Spivey, Jeanne K. Wang, Hui Liu, Andrea Worschech, Marianna Sabatino, Alessandro Monaco, Susan F. Leitman, Andras Falus, Ena Wang, Harvey J. Alter, Francesco M. Marincola

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14 Citations (Scopus)

Abstract

Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether immune cell response to IFN-α is determined directly by race. We compared baseline and IFN-α-induced signal transducer and activator of transcription (STAT)-1, STAT-2, STAT-3, STAT-4, and STAT-5 protein and phosphorylation levels in purified T cells, global transcription, and a genomewide single-nucleotide polymorphism (SNP) profile of healthy AA and EA blood donors. In contrast to HCV-infected individuals, healthy AAs displayed no evidence of reduced STAT activation or IFN-α-stimulated gene expression compared to EAs. Although >200 genes reacted to IFN-α treatment, race had no impact on any of them. The only gene differentially expressed by the two races (NUDT3, P < 10-7) was not affected by IFN-α and bears no known relationship to IFN-α signaling or HCV pathogenesis. Genomewide analysis confirmed the self-proclaimed racial attribution of most donors, and numerous race-associated SNPs were identified within loci involved in IFN-α signaling, although they clearly did not affect responsiveness in the absence of HCV. We conclude that racial differences observed in HCVinfected patients in the responsiveness to IFN-α are unrelated to inherent racial differences in IFN-α signaling and more likely due to polymorphisms affecting the hosts' response to HCV, which in turn may lead to a distinct disease pathophysiology responsible for altered IFN signaling and treatment response.

Original languageEnglish
Pages (from-to)803-808
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number2
DOIs
Publication statusPublished - 15 Feb 2010

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Keywords

  • African-American
  • European American
  • Hepatitis C virus
  • Microarray
  • Signal transducers and activators of transcription

ASJC Scopus subject areas

  • General

Cite this

Pos, Z., Selleri, S., Spivey, T. L., Wang, J. K., Liu, H., Worschech, A., Sabatino, M., Monaco, A., Leitman, S. F., Falus, A., Wang, E., Alter, H. J., & Marincola, F. M. (2010). Genomic scale analysis of racial impact on response to IFN-α. Proceedings of the National Academy of Sciences of the United States of America, 107(2), 803-808. https://doi.org/10.1073/pnas.0913491107