Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis
Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis
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DOI：
10.1016/s0022-510x(01)00573-1
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发表时间：
2001-09-15
影响因子：
4.4
通讯作者：
Cosi, V
中科院分区：
文献类型：
--
作者：
Franciotta, D;Cuccia, M;Cosi, V
通过对 81 名意大利患者和 130 名对照者进行的意大利病例系列分析，我们分析了重症肌无力 (MG) 与 MHC II/III 类区域遗传多态性之间的关联。 TNF-B*1、C4A*Q0、C4B*1、DRB1*03 超型（可能是 8.1 祖先单倍型的一部分）的频率增加在早发 (EO) MG 女性中与对照组相比最大 [p < 0.05，相对风险 (RR) = 9.9]。这些患者既没有表现出明显高频率的胸腺增生，也没有表现出高水平的血清抗乙酰胆碱受体抗体。胸腺瘤患者不存在 DRB1*03 等位基因；然而，与对照组相比，该标志物在 MG 患者中出现频率较高（p < 0.005；RR = 6.2），在女性患者中出现频率较高（p < 0.005；RR = 7.8），在 EOMG 女性患者中出现频率最高（p < 0.005；RR = 15.1）。 TNF-B*1、C4A*Q0、C4B*1、DRB1*03 超型分析。其重组体表明C4和TNF之间的MHC区域可能含有影响女性MG易感性的基因。超型内的多态性标记，例如TNF-B*1 和 C4A*Q0 可能导致女性 MG 患者亚群免疫反应的病理学显着异常，不能排除其他干预基因的综合作用。 (C) 2001 Elsevier Science B.V. 保留所有权利。
With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p < 0.05, relative risk (RR) = 9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p < 0.005; RR = 6.2), more-frequent in females (p < 0.005; RR = 7.8) and most frequent in EOMG female patients (p < 0.005; RR = 15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype. and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients, The combined effect of other intervening genes cannot be excluded. (C) 2001 Elsevier Science B.V. All rights reserved.