Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: Interaction with IL-10 gene polymorphisms

Authors

  • Koko Bate Aborsangaya,

    1. Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Iga Dembinski,

    1. Canadian Blood Services, Winnipeg, Manitoba, Canada
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  • Suresh Khatkar,

    1. Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Martin Prince Alphonse,

    1. Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Peter Nickerson,

    1. Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Canadian Blood Services, Winnipeg, Manitoba, Canada
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  • Julia D. Rempel

    Corresponding author
    1. Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
    • Departments of Internal Medicine and Immunology, University of Manitoba, 804D-715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
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    • Potential conflict of interest: Dr. Rempel received grants from University of Manitoba and CHIR-Institute of Aboriginal Peoples Health.

    • fax: 204-789-3987


Abstract

The host immune response is a critical determinant in viral infection outcome. Epidemiological studies indicate that North American indigenous peoples are more resistant to chronic HCV infection than other populations. Due to the prominence of IL-10 in chronic HCV infection, we investigated the genetic tendency to produce IL-10 in Caucasian (CA) and First Nation (FN) populations. Peripheral blood mononuclear cells (PBMCs) from CA subjects had a greater tendency to produce IL-10 defined by allelic polymorphisms, as well as genotypes and haplotypes, at the -1082, -819, and -592 positions of the IL-10 promoter. More importantly, we directly evaluated the influence of ethnicity on the ability of HCV core protein to induce IL-10 synthesis and found significantly higher IL-10 production by PBMCs isolated from healthy CA subjects compared with FN subjects. Further examination of the underlying relationship between core-induced IL-10 with the high, intermediate, and low phenotypes at the -1082, -819, and -592 position revealed that spontaneous and core-induced IL-10 synthesis tended to interact negatively with defined polymorphisms. This was particularly evident for the FN cohort, in which the relationship was strengthened by a stronger interaction of core with the low–IL-10–producing phenotypes. As with previous studies, concanavalin A induced IL-10 synthesis from the CA cohort positively associated with defined genetic phenotypes. Conclusion: Cells from FN subjects had a reduced capacity to produce IL-10 in response to HCV core protein, suggesting that reduced susceptibility of FN immunity to virally induced IL-10 synthesis might contribute to epidemiological observations of enhanced HCV clearance. (HEPATOLOGY 2007;45:623–630.)

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