Distribution of killer cell immunoglobulin-like receptors in the Greek population

Niokou, Dimitra; Spyropoulou-Vlachou, Maria; Darlamitsou, Areti; Stavropoulos-Giokas, Catherine

doi:10.1016/j.humimm.2003.08.100

Cited by 55 publications

(77 citation statements)

References 38 publications

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“…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.…”

Section: Resultsmentioning

confidence: 69%

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: 69%

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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“…Differences between leukemic patients and controls in the distribution of NKR genes and KIR phenotypes were estimated by w 2 -test, and Yates-corrected P-values (P c ) were subjected to correction for the number of NKR genes analyzed. 26,27 The absolute linkage disequilibrium (D) parameters for pairs of KIR genes were determined using the method of Mattiuz et al 28 The significance of D between the presence of two KIR genes was tested by the w 2 -test (Yates correction).…”

Section: Discussionmentioning

confidence: 99%

“…12,13,24,26,27,29,30 The inhibitory KIR3DL1 for HLA-Bw4 was positive in all patient samples except for one patient with CML. We observed a significantly higher frequency (P c ¼ 0.007) of the inhibitory KIR2DL2 in the total leukemic patient group compared to the controls.…”

Section: Nkr Frequenciesmentioning

confidence: 91%

“…13,24,26,27,29 Phenotype AA1 is composed of seven KIR loci (2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3 and 2DS4). 13,26 In contrast, in the leukemic patients, the prevailing KIR phenotype was AB1 (2DL1, 2DL2, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3, 2DS2 and 2DS4) with 20.8% frequency, which is higher compared to the other Caucasoid populations studied 13,24,26,27 and is significantly increased (31%) in patients with AML (P c ¼ 0.017). Another KIR phenotype AB9 was detected in nine of the 96 patients (9.4%) and was significantly associated with CML patients (P c ¼ 0.020).…”

Section: Specific Kir Phenotype Analysismentioning

confidence: 99%

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Identification of natural killer cell receptor phenotypes associated with leukemia

2004

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Natural killer (NK) cells play a key role in defense against tumor cells that have the capacity to downregulate human leukocyte antigen (HLA) class I expression. It has been reported that leukemic cells can have downregulated expression of HLA class I molecules. The polymorphic nature of NK cell receptor (NKR) genes generates diverse repertoires in the human population, which display specificity in the innate immune response. In the present study, 11 KIR and two CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148 healthy Caucasians. Here, we report a significant increased frequency of the more inhibitory AB killer cell immunoglobulin-like receptor (KIR) phenotype in leukemic patients compared to the controls (31.1% in healthy controls vs 51.0% in leukemic patients, P c ¼ 0.002), which is related to the high prevalence of the inhibitory KIR2DL2 in this population (P c ¼ 0.007). Moreover, two specific KIR phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly associated with leukemic patients. Our study suggests that an important percentage of leukemic patients express a KIR phenotype in favor of escape from NK cell immunity.

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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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Distribution of killer cell immunoglobulin-like receptors in the Greek population

Cited by 55 publications

References 38 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

Identification of natural killer cell receptor phenotypes associated with leukemia

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

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