Premium
Impact of aboriginal ethnicity on HCV core‐induced IL‐10 synthesis: Interaction with IL‐10 gene polymorphisms
Author(s) -
Aborsangaya Koko Bate,
Dembinski Iga,
Khatkar Suresh,
Alphonse Martin Prince,
Nickerson Peter,
Rempel Julia D.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21511
Subject(s) - ethnic group , core (optical fiber) , gene , medicine , genetics , virology , immunology , biology , sociology , physics , anthropology , optics
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. (H EPATOLOGY 2007;45:623–630.)