title: Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: interaction with IL-10 gene polymorphisms.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Koko Bate
authors.initials: KB
authors.lastname: Aborsangaya
authors.forename: Iga
authors.initials: I
authors.lastname: Dembinski
authors.forename: Suresh
authors.initials: S
authors.lastname: Khatkar
authors.forename: Martin Prince
authors.initials: MP
authors.lastname: Alphonse
authors.forename: Peter
authors.initials: P
authors.lastname: Nickerson
authors.forename: Julia D
authors.initials: JD
authors.lastname: Rempel
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus; D006526:Hepatitis C / Q000208:ethnology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007198:Indians, North American / Q000208:ethnology / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D014758:Viral Core Proteins / Q000502:physiology*; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: D008934:Mitogens; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D003208:Concanavalin A; D016753:Interleukin-10