ASSOCIATION OF SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS IN SWEDEN WITH HLA CLASS-II DRB1 AND DQB1 ALLELES
ASSOCIATION OF SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS IN SWEDEN WITH HLA CLASS-II DRB1 AND DQB1 ALLELES
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DOI：
10.1016/0198-8859(94)90099-x
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发表时间：
1994-01-01
期刊：
影响因子：
2.7
通讯作者：
GYLLENSTEN, U
中科院分区：
文献类型：
--
作者：
ALLEN, M;SANDBERGWOLLHEIM, M;GYLLENSTEN, U
通过对94例瑞典复发和缓解患者的DQA 1、DQB 1、DRB 1和DPB 1位点进行基于PCR的分型，研究MS与HLA II类等位基因的相关性。单倍型DRB 1 *1501-DQA 1 * O 102-DQB 1 *0602被发现与MS正相关，并且发现三种单倍型与MS负相关。连锁不平衡使得难以评估DRB 1或DQB 1在疾病关联中是否起主要作用，而与DPB 1和DQA 1的关联似乎继发于DQB I和DRB 1。与MS负相关的三种单倍型中的两种携带DQB 1 *0301等位基因。此外，负相关的DRB 1 *0401-DQA 1 *0301-DQB 1 *0301单倍型与非相关的DRB 1 *0401-DQA 1 *0301-DQB 1 *0302单倍型仅在DQB 1处不同。这些结果表明，DQB 1等位基因，以及一些DRB 1等位基因，参与MS的易感性和保护。在寻找序列基序的DR β链与MS易感性，所有DRB 1等位基因的单倍型正相关的MS，包括DRB 1 *1501，被发现编码一个瓦尔在DR β链的位置86。此外，与MS负相关的DRB 1等位基因都编码位置86处的Gly，表明位置86处的残基可能在赋予对MS的易感性和保护方面是关键的。最后，当去除DRB 1 *1501单倍型的影响时，没有支持MS与推定的DQ-α β异二聚体相关的假设，由某些DQA 1和DQB 1等位基因编码。
The association of MS with HLA class II alleles was studied by PCR-based typing of the DQA1, DQB1, DRB1, and DPB1 loci in 94 Swedish patients with relapses and remissions of the disease. The haplotype DRB1*1501-DQA1*O102-DQB1*0602 was found to be positively associated and three haplotypes were found to be negatively associated with MS. Linkage disequilibrium makes it difficult to assess whether DRB1 or DQB1 plays the primary role in the disease association, while the association with DPB1 and DQA1 appears to be secondary to that of DQB I and DRB1. Two of the three haplotypes negatively associated with MS carry the DQB1*0301 allele. Also, the negatively associated DRB1*0401-DQA1*0301-DQB1*0301 haplotype differs from those with nonassociated DRB1*0401-DQA1*0301-DQB1*0302 haplotype only at DQB1. These results suggest that DQB1 alleles, as well as some DRB1 alleles, are involved in susceptibility and protection to MS. In searching for sequence motifs in the DR beta chain associated with MS susceptibility, all DRB1 alleles on haplotypes positively associated with MS, including the DRB1*1501, were found to encode a Val at position 86 of the DR beta chain. Also, DRB1 alleles that are negatively associated with MS all encode a Gly at position 86, suggesting that the residue at position 86 may be critical in conferring susceptibility and protection to MS. Finally, when the effect of the DRB1*1501 haplotype was removed there was no support for the hypothesis that MS is associated with a putative DQ-alpha beta heterodimer, encoded for by certain DQA1 and DQB1 alleles.