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

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 gene...

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Published in:	Hepatology (Baltimore, Md.) Vol. 45; no. 3; pp. 623 - 630
Main Authors:	Aborsangaya, Koko Bate, Dembinski, Iga, Khatkar, Suresh, Alphonse, Martin Prince, Nickerson, Peter, Rempel, Julia D.
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2007 Wiley
Subjects:	Adult Biological and medical sciences Cells, Cultured Concanavalin A - pharmacology European Continental Ancestry Group - ethnology European Continental Ancestry Group - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation Hepacivirus Hepatitis C - ethnology Hepatitis C - immunology Hepatitis C - metabolism Human viral diseases Humans Immunity, Innate Indians, North American - ethnology Indians, North American - genetics Infectious diseases Interleukin-10 - genetics Interleukin-10 - metabolism Male Medical sciences Middle Aged Mitogens - pharmacology Monocytes - metabolism Monocytes - pathology Polymorphism, Single Nucleotide Viral Core Proteins - physiology Viral diseases Viral hepatitis Infection Chronic Synthesis Viral disease Gastroenterology Interleukin 10 Digestive diseases Hepatic disease Viral hepatitis C Polymorphism
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Summary:	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.)
Bibliography:	fax: 204‐789‐3987 Potential conflict of interest: Dr. Rempel received grants from University of Manitoba and CHIR‐Institute of Aboriginal Peoples Health. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0270-9139 1527-3350
DOI:	10.1002/hep.21511