Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility
Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility
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DOI：
10.1038/sj.gene.6364333
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发表时间：
2006-10-01
影响因子：
5
通讯作者：
Young, N. T.
中科院分区：
文献类型：
--
作者：
Jones, D. C.;Edgar, R. S.;Young, N. T.
杀伤免疫球蛋白样受体（KIR）在自然杀伤细胞和一些T细胞亚群上表达，并且在与靶细胞上的适当人白细胞抗原（HLA）配体结合后产生激活或抑制信号。最近的遗传关联研究表明，KIR基因型与几种炎症性疾病的发生有关。溃疡性结肠炎（UC）是由宿主细菌植物群驱动的免疫系统的不适当激活引起的结肠粘膜的炎性病症。我们开发了一种基于聚合酶链反应-序列特异性引物（SSP）的检测方法，对194名UC患者和216名对照个体进行14个KIR基因、KIR 2D受体的HLA-Cw配体表位和凝集素样激活受体NKG 2D的多态性的基因分型。初步分析发现，UC队列中KIR 2DL 2和-2DS2的表型频率显著增加（分别为P = 0.030和0.038）。Logistic回归分析显示，在其配体HLA-Cw组1存在下，KIR 2DL 3赋予的保护作用（P = 0.019）。提示KIR基因型和HLA配体相互作用可能与UC的遗传易感性有关。
Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. Ulcerative colitis (UC) is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by host bacterial flora. We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P = 0.030 and 0.038, respectively). Logistic regression analysis revealed a protective effect conferred by KIR2DL3 in the presence of its ligand HLA-Cw group 1 (P = 0.019). These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC.