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Association of CD94/NKG2A, CD94/NKG2C, and its ligand HLA-E polymorphisms with Behcet's disease.

Authors
Seo, J; Park, JS; Nam, JH; Bang, D; Sohn, S; Lee, ES; Park, KS
Citation
Tissue antigens, 70(4):307-313, 2007
Journal Title
Tissue antigens
ISSN
0001-28151399-0039
Abstract
Inhibitory CD94/NKG2A and activating CD94/NKG2C receptors are expressed on natural killer, CD4, and CD8 T cells and recognize human leukocyte antigen (HLA)-E, resulting in the modulation of cytotoxic activity and cytokine production. An imbalance in cytotoxic activity and cytokine production has been implicated in Behcet's disease (BD). The results of this study showed that the NKG2A c.-4258*C, c.338-90*G, and CD94 c.-134*T alleles (P= 0.015, OR = 0.8; P < 0.0001, OR = 0.5; and P= 0.034, OR = 0.8, respectively) were associated with decreased risk and that NKG2A c.284-67_-62del, c.1077*C, and the activating receptor, NKG2C c.305*T were not associated with 345 patients with BD. But a significant difference in NKG2C c.305*T was detected among BD patients with ocular lesions and arthritis (P < 0.0001, OR = 2.1 and P= 0.0001, OR = 1.8, respectively). We already showed in our previous research that HLA-E*0101 also appears to contribute to a reduction in risk through the inhibitory CD94/NKG2A-mediated immune response. This result led us to the analyses of the combined risk of the HLA-E and the NKG2A for BD. Individuals harboring HLA-E*0101, NKG2A c.-4258*C, and c.338-90*G evidenced a reduced risk of BD compared with healthy controls (21.1% vs 40.1%, P < 0.0001, OR = 0.4). By way of contrast, individuals without the HLA-E*0101, NKG2A c.-4258*C, and c.338-90*G alleles evidenced a twofold increased risk of BD (P= 0.014, OR = 2.0). Individuals without HLA-E*0101, NKG2A c.-4258*G/*G, and c.338-90*G evidenced a 4.8-fold increase in BD risk (P= 0.0002, OR = 4.8). Although the effects of these single nucleotide polymorphisms (SNPs) remain unclear, our results indicate that the SNPs of the inhibitory receptor CD94/NKG2A and its haplotypes, as well as its ligand HLA-E, are associated with BD immune systems.
MeSH terms
AllelesBehcet Syndrome/genetics*Behcet Syndrome/immunologyBehcet Syndrome/metabolismCD8-Positive T-Lymphocytes/immunology*CD8-Positive T-Lymphocytes/metabolismCase-Control StudiesCohort StudiesFemaleGenetic Predisposition to DiseaseHLA Antigens/genetics*HLA Antigens/immunologyHLA Antigens/metabolismHistocompatibility Antigens Class I/genetics*Histocompatibility Antigens Class I/immunologyHistocompatibility Antigens Class I/metabolismHumansKiller Cells, Natural/immunology*Killer Cells, Natural/metabolismLigandsMaleNK Cell Lectin-Like Receptor Subfamily D/genetics*NK Cell Lectin-Like Receptor Subfamily D/immunologyNK Cell Lectin-Like Receptor Subfamily D/metabolismPolymorphism, Single Nucleotide*
DOI
10.1111/j.1399-0039.2007.00907.x
PMID
17767552
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
AJOU Authors
손, 성향이, 은소
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