Stewart G J, Teutsch S M, Castle M, Heard R N, Bennetts B H
Department of Immunology, Westmead Hospital, New South Wales, Australia.
Eur J Immunogenet. 1997 Apr;24(2):81-92. doi: 10.1046/j.1365-2370.1997.00252.x.
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 DRB11501, DQB10602 and DQA10102, 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 DQA10101. Associations were found with DQB1 alleles sharing sequence homology with DQB10602, 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 DRB11501, DQB10602, DQA10102 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.
对100例复发/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进行分子基因分型，结果表明其与HLA - DR2、DQw6相关等位基因DRB11501、DQB10602和DQA10102存在关联，从而将这一在多个国家MS患者中的发现扩展至澳大利亚人群。通过相对易感性效应（RPE）方法分析，未发现DQA1或DQB1存在第二个易感等位基因的证据。然而，我们的数据以及其他研究的数据表明与DQA10101呈负相关。发现与与DQB10602具有序列同源性的DQB1等位基因、在第26位残基编码亮氨酸（Leu 26）的DQB1等位基因、在第34位残基编码谷氨酰胺（Gln 34）的DQA1等位基因以及Leu 26加Gln 34等位基因存在关联，但双位点连锁分析表明，每一种关联均继发于DRB11501、DQB10602、DQA10102的关联。尽管在第25位氨基酸处有苯丙氨酸减少的趋势，但本研究未发现最近报道的与在第25位氨基酸编码苯丙氨酸、第69位氨基酸编码亮氨酸和第52位氨基酸编码精氨酸的DQA1等位基因的负相关。尽管MHC分型取得了重大进展，但在分子水平上确定这些等位基因在全球范围内关联的解释仍然难以捉摸。
