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Host immunogenetics and control of human herpesvirus-8 infection

  1. Author:
    Brown, E. E.
    Fallin, M. D.
    Goedert, J. J.
    Hutchinson, A.
    Vitale, F.
    Lauria, C.
    Giuliani, M.
    Marshall, V.
    Mbisa, G.
    Serraino, D.
    Messina, A.
    Durum, S.
    Whitby, D.
    Chanock, S. J.
    Kaposi Sarcoma Genetics Working Group

  2. Author Address

    NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NCI, SAIC Frederick Inc, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NCI, SAIC Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe Alessand, Palermo, Italy. Lega Italiana Lotta Contro & Tumori, Sez Ragusa, Ragusa, Italy. Ist Super Sanita, Reparto Epidemiol, Dipartimento Malattie Infett Parassitarie & Immun, I-00161 Rome, Italy. Natl Canc Inst, Epidemiol Unit, Aviano, Italy. Univ Catania, Dipartimento Sci Biomed, I-95124 Catania, Italy.;Brown, EE, NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8005 MSC 7248, Rockville, MD 20852 USA.;brownbe@mail.nih.gov
    1. Year: 2006
    2. Date: Apr
  2. Journal: Journal of Infectious Diseases
    1. 193
    2. 8
    3. Pages: 1054-1062
  4. Type of Article: Article
  5. ISSN: 0022-1899
  1. Abstract:

    Background. Kaposi sarcoma (KS) is primarily caused by human herpesvirus (HHV)-8 infection, and the risk is increased with high HHV-8 lytic or latent antibody titers or the detection of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). Host genes important for control of HHV-8 infection are not well characterized. Methods. In 172 HHV-8 latent nuclear antigen ( LANA)-seropositive adults in Italy without KS, we examined correlations of common variants in host immune genes with the detection of HHV-8 DNA in PBMCs and with high lytic and latent antibody titers. Twenty-eight single-nucleotide polymorphisms in 14 genes were analyzed. We detected HHV-8 DNA in PBMCs with real-time amplification of the K6 gene, anti-K8.1 ( lytic) titers with enzyme-linked immunosorbent assay, and anti-LANA ( latent) titers with immunofluorescence. Results. Detection of HHV-8 DNA in PBMCs was not significantly related to any variant examined. In contrast, a 3-locus haplotype of IL4, which contains the -1098G allele ( rs2243248), was overrepresented among subjects with high lytic titers ( odds ratio [ OR], 2.8 [ 95% confidence interval {CI}, 1.1-6.7]), compared with those with low titers, as was the functional promoter variant of IL6, C-236C ( rs1800795) ( OR, 3.7 [ 95% CI, 1.1-12.8]). Compared with subjects with low HHV-8 latent antibody titers, analysis of inferred haplotypes for IL12A revealed an overrepresentation of -798T/277A in subjects with high HHV-8 latent antibody titers ( OR, 2.4 [ 95% CI, 1.1-5.2]). Conclusions. Our observations are the first to provide preliminary evidence suggesting that common variants in key host immune genes could influence the control of HHV-8 infection.

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External Sources

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  2. DOI: 10.1086/501470
  3. PMID: 16544245
  4. View record in Web of Science®
  5. WOS: 000236102200002

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