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

Abstract

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 (n¼93, population controls) and Aboriginal (n¼86) 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.

Hepatitis C Virus in American Indian/Alaskan Native and Aboriginal Peoples of North America

“…Genetic studies by our lab and others indicate that Manitoban FN and Métis populations have a reduced genetic tendency to produce IL-10 compared to non-Aboriginals [70,71]. Moreover, we found that PBMC from virally-naïve FN individuals produced significantly less IL-10 in response to HCV core protein than cells isolated from non-FN individuals, suggesting that FN cells were not as susceptible to immune deregulation upon first encounter with the virus [70,72]. …”

“…The disparities in KIR gene profiles of virally naïve Aboriginals as compared to non-Aboriginals paralleled these disparities reported for better as compared to worse outcomes for HCV infection, suggesting the further involvement of biological processes in racial trends of HCV chronicity [72]. Coincidently, the unique KIR gene profile and genotypes of Manitoban Aboriginals were similar to other KIR analyses performed within indigenous peoples throughout the Americas; whereas, data from Manitoban Caucasians reflected that of Caucasian globally [72]. This might be accounted for by a common ancestry or an abrupt immune selection such as the “old world” disease epidemics that swept through indigenous communities [75,76,77,78].…”

“…Unique KIR gene profiles consisting of a greater presence of activatory genes have been published for patients with self-limited or benign HCV infection outcomes relative to patients with deteriorated disease courses [73,74]. The disparities in KIR gene profiles of virally naïve Aboriginals as compared to non-Aboriginals paralleled these disparities reported for better as compared to worse outcomes for HCV infection, suggesting the further involvement of biological processes in racial trends of HCV chronicity [72]. Coincidently, the unique KIR gene profile and genotypes of Manitoban Aboriginals were similar to other KIR analyses performed within indigenous peoples throughout the Americas; whereas, data from Manitoban Caucasians reflected that of Caucasian globally [72].…”

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…[131]. Recent studies suggest unique host immunity may enhance spontaneous clearance of HCV in certain Aboriginal populations [137][138]. One study compared…”

Comparison of KIR gene content profiles revealed a difference between northern and southern Persians in the distribution of KIR2DS5 and its linked loci

“…Because KIR3DS1, 2DS1, and 2DS5, as well as 2DL5A, are linked together as the T4 cluster at the telomeric half of the KIR gene complex, we compared the carrier frequency of individuals carrying this gene cluster between the northern and southern Persian populations and observed a significant increase of T4 gene clusters in northern Persians compared with southern Persians (p ϭ 0.03; Table 2). Further comparison with world populations reveals that the T4 gene cluster occurs at high frequencies in Amerindian populations, such as Yucpa (74%), Amazonian (67.5%), Tarahumara (66.1%), Canadian Aboriginal (65.3%), and Purepecha (62.2%), as well as in southern Indian populations (60%) [20,23,29,30].…”