Marin M L C, Savioli C R, Yamamoto J H, Kalil Jorge, Goldberg A C
Laboratory of Immunology, Heart Institute-InCor, School of Medicine, University of São Paulo, São Paulo, Brazil.
Eur J Immunogenet. 2004 Apr;31(2):63-71. doi: 10.1111/j.1365-2370.2004.00446.x.
The major histocompatibility complex (MHC) class I chain-related A (MICA) gene, located near HLA-B, codes for protein products with structural similarities to those of classical MHC class I genes, but which neither bind beta(2)-microglobulin nor present peptide. Expressed predominantly on gastrointestinal and tumour epithelial cells, they are stress-induced and interact with C-type lectin like receptor (NKG2D) on gammadelta, alphabeta CD8+ T cells and natural killer (NK) cells. MICA is highly polymorphic, with 54 extracellular allelic sequences described. We typed 200 healthy subjects in a sample of the São Paulo population by extended polymerase chain reaction-sequence-specific primers (PCR-SSP) to characterize the MICA polymorphism and analysed MICA/HLA-B linkage disequilibrium. The MICA008 group (g) was predominant (47%), with several HLA-B associations. Rare combinations MICA008g-HLA-B37, MICA008g-B72 and MICA010-HLA-B52 were detected. Given the extent of this polymorphism and its possible relevance for disease association, we determined MICA and HLA-B alleles in 33 Behçet's patients, in an attempt to clarify the associated genetic marker. Our results showed an increase of MICA006, but not MICA009, in the patient group (6/33) compared with controls (3/200) (18.2% vs. 1.5%; P(c) = 0.005). Both alleles were always in association with HLA-B51, suggesting that HLA-B is indeed the primary susceptibility locus (P = 0.00008) and that MICA*006 may be an additional risk factor.
主要组织相容性复合体（MHC）I类链相关A（MICA）基因位于HLA - B附近，其编码的蛋白质产物在结构上与经典MHC I类基因的产物相似，但既不结合β2-微球蛋白，也不呈递肽段。MICA主要在胃肠道和肿瘤上皮细胞上表达，受应激诱导，并与γδ、αβ CD8 + T细胞和自然杀伤（NK）细胞上的C型凝集素样受体（NKG2D）相互作用。MICA具有高度多态性，已描述了54种细胞外等位基因序列。我们通过扩展聚合酶链反应 - 序列特异性引物（PCR - SSP）对圣保罗人群样本中的200名健康受试者进行基因分型，以表征MICA多态性，并分析MICA / HLA - B连锁不平衡。MICA008组（g）占主导地位（47%），与多种HLA - B存在关联。检测到罕见组合MICA008g - HLA - B37、MICA008g - B72和MICA010 - HLA - B52。鉴于这种多态性的程度及其与疾病关联的潜在相关性，我们测定了33例白塞病患者的MICA和HLA - B等位基因，试图阐明相关的遗传标记。我们的结果显示，与对照组（3/200）相比，患者组（6/33）中MICA006增加，但MICA009未增加（18.2%对1.5%；P(c)=0.005）。这两个等位基因总是与HLA - B51相关联，表明HLA - B确实是主要的易感位点（P = 0.00008），而MICA*006可能是一个额外的风险因素。
