The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

Genetic differences in immune regulators influence disease resistance and susceptibility patterns. There are major health discrepancies in immune-mediated diseases between Caucasians and Canadian Aboriginal people, as well as with other indigenous people of the Americas. Environmental factors offer...

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Bibliographic Details
Published in:	European journal of human genetics : EJHG Vol. 19; no. 12; pp. 1276 - 1280
Main Authors:	REMPEL, Julia D, HAWKINS, Kim, LANDE, Erin, NICKERSON, Peter
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing Group 01-12-2011
Subjects:	Adult Aged Arthritis Autoimmune diseases Biological and medical sciences Canada - ethnology Centromere - genetics Chronic infection Continental Population Groups - genetics Cytokines Diabetes Disease Disease resistance Disease Resistance - genetics Environmental factors Ethnicity Female Fundamental and applied biological sciences. Psychology Gene Expression Profiling Gene Frequency General aspects. Genetic counseling Genes Genetic Predisposition to Disease Genetics Genetics of eukaryotes. Biological and molecular evolution Genotypes Haplotypes Hepatitis Hepatitis C Hepatitis C virus Hepatology Humans Immunoglobulin-like receptors Immunoglobulins Immunology Immunomodulation Infections Male Medical genetics Medical sciences Middle Aged Molecular and cellular biology Native North Americans Phenotypes Population Receptors, KIR - genetics Selection, Genetic - immunology Telomere - genetics White people Young Adult Canada North America America Americas Manitoba Canada Disease ethnicity Aboriginal Cluster Genetics KIR telomeric Immunity KIR centromeric pro-inflammatory immunity Ethnic group Profile
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Summary:	Genetic differences in immune regulators influence disease resistance and susceptibility patterns. There are major health discrepancies in immune-mediated diseases between Caucasians and Canadian Aboriginal people, as well as with other indigenous people of the Americas. Environmental factors offer a limited explanation as Aboriginal people also demonstrate a rare resistance to chronic hepatitis C virus infection. Killer immunoglobulin-like receptors (KIRs) are known modulators of viral responses and autoimmune diseases. The possibility that variation in KIR cluster profiles contribute to the health outcomes of Aboriginal people was evaluated with Canadian Caucasian (n=93, population controls) and Aboriginal (n=86) individuals. Relative to Caucasians, the Aboriginal KIR cluster displayed a greater immune activating phenotype associated with genes of the B haplotype situated within the telomeric region. In conjunction, there was a decrease in the genes of the B haplotype from the centromeric region. Caucasian and Aboriginal cohorts further demonstrated distinct genotype and haplotype relationships enforcing the disconnect between the B haplotype centromeric and telomeric regions within the Aboriginal population. Moreover, Caucasian KIR cluster patterns reflected studies of Caucasians globally, as well as Asians. In contrast, the unique pattern of the Canadian Aboriginal cohort mirrored the phenotype of other indigenous peoples of the Americas, but not that of Caucasians or Asians. Taken together, these data suggest that historically indigenous peoples of the Americas were subject to immune selection processes that could be influencing the current disease resistance and susceptibility patterns of their descendents.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1018-4813 1476-5438
DOI:	10.1038/ejhg.2011.114