HLA-DR, -DQA1 and -DQB1 associations in Australian multiple sclerosis patients.
HLA-DR, -DQA1 and -DQB1 associations in Australian multiple sclerosis patients.
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澳大利亚多发性硬化症患者的 HLA-DR、-DQA1 和 -DQB1 关联。
DOI：
10.1046/j.1365-2370.1997.00252.x
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
B. Bennetts
中科院分区：
文献类型：
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作者：
G. Stewart;S. Teutsch;M. Castle;R. Heard;B. Bennetts
对 100 名复发/缓解型多发性硬化症 (MS) 患者的主要组织相容性复合体 (MHC) II 类基因座 HLA-DRB1、-DQB1 和 -DQA1 进行的分子基因分型表明与 HLA-DR2、DQw6 相关等位基因 DRB1*1501、DQB1*0602 和 DQA1*0102 相关，从而将这一发现扩展到多发性硬化症患者遍布多个国家和澳大利亚。通过相对易感效应 (RPE) 方法进行的分析没有提供 DQA1 或 DQB1 上第二个易感性等位基因的证据。然而，我们和其他人的数据表明与 DQA1*0101 呈负相关。发现 DQB1 等位基因与 DQB1*0602 具有序列同源性，DQB1 等位基因在残基 26 编码亮氨酸 (Leu 26)，DQA1 等位基因在残基 34 (Gln 34) 编码谷氨酰胺，以及与 Leu 26 加 Gln 34 等位基因存在关联，但通过双基因座连锁分析显示，每个等位基因都是 DRB1*1501 的次要序列， DQB1*0602、DQA1*0102 关联。最近报道的 DQA1 等位基因与编码氨基酸 25 的苯丙氨酸、氨基酸 69 的亮氨酸和氨基酸 52 的精氨酸呈负相关，但在这项研究中并未发现，尽管氨基酸 25 的苯丙氨酸有减少的趋势。尽管 MHC 分型取得了重大进展，但在分子水平上确定与这些等位基因的全球关联的解释仍然难以捉摸。
Molecular genotyping for the major histocompatibility complex (MHC) class II loci, HLA-DRB1, -DQB1 and -DQA1, in 100 patients with relapsing/remitting multiple sclerosis (MS) demonstrated an association with the HLA-DR2, DQw6-associated alleles DRB1*1501, DQB1*0602 and DQA1*0102, thereby extending this finding among MS patients in several countries to an Australian population. Analysis by the relative predispositional effect (RPE) method provided no evidence for a second susceptibility allele at either DQA1 or DQB1. However, our data and that of others suggest a negative association with DQA1*0101. Associations were found with DQB1 alleles sharing sequence homology with DQB1*0602, with DQB1 alleles encoding leucine at residue 26 (Leu 26), with DQA1 alleles encoding glutamine at residue 34 (Gln 34) and with Leu 26 plus Gln 34 alleles, but each was shown by two-loci linkage analysis to be secondary to the DRB1*1501, DQB1*0602, DQA1*0102 association. The recently reported negative association with DQA1 alleles encoding phenylalanine at amino acid 25, leucine at amino acid 69 and arginine at amino acid 52 was not found in this study, although there was a trend towards reduced phenylalanine at amino acid 25. The determination at a molecular level of an explanation for the world-wide association with these alleles remains elusive despite major advances in MHC typing.