Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behcet's disease
Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behcet's disease
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DOI：
10.1111/j.1365-3083.2006.01780.x
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发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Julià, M. R.
中科院分区：
文献类型：
--
作者：
Muñoz-Saá, I.;Cambra, A.;Julià, M. R.
白塞氏病（BD）的病因尚不清楚，但涉及遗传和环境因素。HLA-B*51被认为是一种易感性标志物，一些云母等位基因也与此相关。细胞毒性T淋巴细胞已被认为是BD病变的原因，通过NKG 2D表面分子与云母结合。在本研究中，HLA-B和云母等位基因分型聚合酶链反应使用序列特异性引物，在165名健康的西班牙对照和42 BD患者。在健康人群中，云母 *008（28.48%）、云母 *004（17.58%）、云母 *002（14.24%）和云母 *009（9.39%）为优势等位基因，最常见的单倍型为云母 *004-B*44（12.12%）。云母 *001（5.15%）、云母 *004、云母 *011（4.54%）和云母 *018（5.15%）的发生率较高，云母 *010（1.81%）和云母 *008的发生率较低。在北非的个体中也报告了类似的结果，这可能支持两个种群共同祖先起源的假设。与对照组相比，我们的BD患者中云母 *009和云母 *019的频率显着增加：分别为22.62%和9.39%以及10.71%和1.81%。云母 *019的增加在其他BD队列中未被描述，这证实了BD患者云母基因座的遗传异质性。NKG 2D的高亲和力云母等位基因在对照组中的频率高于患者。此外，在纯合子BD患者中未发现高亲和力等位基因。这些结果反驳了BD患者通过MICA-NKG 2D相互作用产生自身攻击性反应的假设。
The aetiology of Behcet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.