Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus

Leland J. Yee, Yong Ming Tang, David E. Kleiner, Dai Wang, KyungAh Im, Abdus Wahed, Xiaomei Tong, Shannon Rhodes, Xiaowen Su, R. Margaret Whelan, Robert J. Fontana, Marc G. Ghany, Brian Borg, T. Jake Liang, Huiying Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR), transforming growth factor-β1 (TGF-β), interleukin-10 (IL-10), and interferon-gamma (IFN-γ), were evaluated for associations with liver fibrosis in 374 treatment-naive patients with genotype-1 chronic HCV infection [194 Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic haplotype approach. Among the 18 haplotypes that occurred with a frequency ≥5% in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T) (abbreviated Mx1-CAGT), and PKR-(+110T)-(+7949G)-(+13846A)-(+22937Tj-(+40342T) (abbreviated PKR-TGATT) haplotypes were independently associated with less severe hepatic fibrosis (Ishak ≥ 3 versus s) = 0.6)], and race (for Mx1-CAGT: OR = 0.33; 95% CI: 0.16-0.68; P = 0.0027; and for PKR-TGATT: OR = 0.56; 95% CI: 0.32-0.98; P = 0.0405). Population structure was evaluated using the structured association method using data from 161 ancestry-informative markers and did not affect our findings. We used an independent cohort of 34 AA and 160 CA in an attempt to validate our findings, although notable differences were found in the characteristics of the two patient groups. Although we observed a similar protective trend for the Mx1-CAGT haplotype in the validation set, the association was not statistically significant. Conclusion: In addition to other factors, polymorphisms in cytokine genes may play a role in the progression of HCV-related fibrosis; however, further studies are needed.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalHepatology
Volume46
Issue number1
DOIs
StatePublished - Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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