KIR Gene in Ethnic and Mestizo Populations from Mexico

Gutiérrez-Rodrı́guez, Margarita; Sandoval-Ramírez, Lucila; Díaz‐Flores, Margarita; Marsh, Steven G.E.; Valladares‐Salgado, Adán; Madrigal, J. Alejandro; Mejı́a-Aranguré, Juan Manuel; García, Celsa; Huerta‐Zepeda, Alejandra; Ibarra-Cortés, Bertha; Ortega-Camarillo, Clara; Crúz, Miguel A.

doi:10.1016/j.humimm.2005.11.007

Cited by 56 publications

(65 citation statements)

References 41 publications

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“…In addition, KIR2DL1, KIR2DL3, KIR2DS4 and KIR3DL1 genes within the A haplotype were present in over 84% of all individuals, a finding paralleled in other ethnic groups (Table 1; see Supplementary Table 1 for gf differences between Manitoban populations and details regarding the presence of KIR2DL5A and KIR2DL5B in these cohorts). [19][20][21][22] Conversely, marked variation was apparent in the genes associated with the B haplotype. Compared with Caucasian samples, the Aboriginal population exhibited a decreased presence of B haplotype centromeric genes KIR2DL2, KIR2DS2, as well as KIR2DS3 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The gene pattern from the Caucasian cohort paralleled Caucasians from other continents; 19,23 whereas, the Aboriginal gene profile bore similarity to patterns from other indigenous peoples of the Americas. 19,20 The resemblance was particularly acute with respect to the genes from the B haplotype. As with the Aboriginal population, the reduced presence of the B centromeric genes, coupled with the prominence of the B telomeric genes was also observed in other American indigenous peoples.…”

Section: Resultsmentioning

confidence: 99%

“…Haplotype designations were made as previously detailed. 19,20 (1) Framework genes were recognized as homozygous. (2) For the centromeric portion of the cluster, as KIR2DL3 and KIR2DL2 are thought to be alleles of the same locus, if only one was present, then that allele was assumed to be homozygous and the centromeric portion was assumed to be an AA or BB haplotype, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…This hierarchy was comparable to the Mexican Purepecha and Tarahumara, and Argentinean Chiriguanos. 19,20 Interestingly, all the indigenous populations, including the Huichol and Wichis, had an increased presence of genotypes 4 and/or 8 that possess genes belonging within the B telomeric segment. This occurred simultaneously to a muted presence of genotypes 2 and 3 with limited connections to the B telomeric segment.…”

Section: Manitoban Aboriginal Genotypes Parallel Those Of Other Amerimentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Manitoban Aboriginal Genotypes Parallel Those Of Other Amerimentioning

confidence: 99%

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

et al. 2011

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“…52 PCR-SSOP was carried out to confirm the presence or absence of KIR genes in Northern and Republic of Ireland populations as previously described. KIR gene and genotype frequencies of an additional 36 global population (4218 individuals from 38 different studies) were obtained from the published literature (35 populations [31][32][33]46,48,49,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] ) and from an online database www.allelefrequencies.net. 72 Genotypes were classified as follows: the absence of 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3 or 2DS5 indicates that an individual is homozygous for the A genotype (that is, AA).…”

Section: Kir Typingmentioning

confidence: 99%

Receptor systems controlling natural killer cell function are genetically stratified in Europe

et al. 2009

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Natural killer (NK) cells are components of the innate immune system that function in identifying and destroying aberrant or pathogen-infected cells. These functions are largely controlled by killer cell immunoglobulin-like receptors (KIRs). KIRs inhibit and activate NK cell functions through interactions with their ligands, epitopes encoded by human leukocyte antigen (HLA) class I genes (HLA-C1, C2 and Bw4). Genes that encode KIR and their HLA ligands vary in frequency across human populations. Here, we characterize two Irish populations for KIR and HLA and determine the spatial distribution of functionally important KIR:HLA systems in Europe, a region known for its considerable underlying genetic stratification. We find that Southern Europe is a region characterized by higher frequencies of activatory KIR and strong inhibitory HLA ligand systems (2DL1:HLA-C2 and 3DL1:Bw4). A lower frequency of activatory KIR and the predominance of a comparatively weaker inhibitory ligand system (2DL3:HLA-C1) are observed northwards. Despite contrasting KIR:HLA systems in Northern and Southern Europe, there is a clear balance between inhibitory and activatory repertoires, and their ligands in both regions. These findings show 'functional stratification' of the epistatic KIR:HLA receptor system in Europe, the presence of which will likely affect NK cell-mediated immunity across different populations.

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Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans

et al. 2006

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Interactions between inhibitory killer cell immunoglobulin-like receptors (iKIR) and human leukocyte antigen (HLA) class I molecules regulate natural killer (NK) cell responses to eliminate infected and transformed cells while maintaining tolerance to healthy cells. Unlinked polymorphic gene families encode KIR receptors and HLA class I ligands and their independent segregation results in a variable number and type of iKIR + HLA pairs inherited in individuals. The diversity in the co-inheritance of iKIR + HLA pairs and activating KIR (aKIR) genes in 759 unrelated individuals from four ethnic populations was analyzed. Every individual studied inherited a minimum of one iKIR + HLA pair; suggesting that major histocompatibility complex class I-dependent inhibitory KIR signaling is essential for human NK cell function. In contrast, 13.4% of the study group lacked all aKIR genes. Twenty percent of the study group carried only one of the four iKIR + HLA pairs. Interestingly, 3% of the study group carrying only KIR2DL3 + HLA-C1 as an iKIR + HLA pair lacked aKIR genes. These data suggest that a single iKIR can constitute the minimal KIR repertoire for human NK cells. Genotypes carrying an equal number of iKIR + HLA pairs and aKIR genes represented 20% of the study group. The remaining individuals had either a dominant inhibitory KIR genotype (iKIR + HLA > aKIR) or a dominant activating KIR genotype (iKIR + HLA < aKIR). Genotypes encoding these imbalanced inhibitory and activating interactions may contribute to susceptibility or resistance to human diseases.

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KIR Gene in Ethnic and Mestizo Populations from Mexico

Cited by 56 publications

References 41 publications

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

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

Receptor systems controlling natural killer cell function are genetically stratified in Europe

Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans

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