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Interaction between RANTES Promoter Variant and CCR5 Delta 32 Favors Recovery from Hepatitis B

  1. Author:
    Thio, C. L.
    Astemborski, J.
    Thomas, R.
    Mosbruger, T.
    Witt, M. D.
    Goedert, J. J.
    Hoots, K.
    Winkler, C.
    Thomas, D. L.
    Carrington, M.

  2. Author Address

    Thomas, Rasmi, Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Thio, Chloe L.; Astemborski, Jacquie, Mosbruger, Timothy, Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. [Witt, Mallory D.] Univ Calif Med Ctr, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90509 USA. [Witt, Mallory D.] David Geffen Sch Med, Los Angeles, CA 90509 USA. [Goedert, James J.] NCI, Viral Epidemiol Branch, Div Cancer Epidemiol & Genet, Rockville, MD 20852 USA. [Hoots, Keith] Univ Texas Hlth Sci Ctr Houston, Gulf States Hemophilia Ctr, Houston, TX 77030 USA. [Winkler, Cherie] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
    1. Year: 2008
  2. Journal: Journal of Immunology
    1. 181
    2. 11
    3. Pages: 7944-7947
  4. Type of Article: Article
  1. Abstract:

    Recovery from acute hepatitis B virus (HBV) infection occurs in 95% of adult-acquired infections. A 32-bp deletion in CCR5 (CCR5 Delta 32), which encodes for a nonfunctional receptor, increases the likelihood of recovery. Using 181 subjects with persistent HBV infection and 316 who had recovered, we tested the hypothesis that an epistatic interaction between functional polymorphisms in RANTES (a CCR5 ligand) and CCR5 impacts recovery. Specific models designed to assess individual contributions of compound genotypes demonstrated that the only combination associated with recovery from an HBV infection was RANTES -403A with CCR5 Delta 32 (odds ratio 0.36, p = 0.02). Because the phenotypic consequence of -403A is reported to be higher levels of RANTES, we propose a model in which excess RANTES in combination with low CCR5 favors recovery from an HBV infection, which will require validation through functional testing. The Journal of Immunology, 2008, 181: 7944-7947.

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