HLA-DRB1和DQA1基因以及DRβ1链功能域中氨基酸多态性在多发性硬化症中的重要性。

Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DR beta 1 chain in multiple sclerosis.

作者信息

Ghabanbasani M Z, Gu X X, Spaepen M, Vandevyver C, Raus J, Marynen P, Carton H, Cassiman J J

机构信息

Center for Human Genetics, University of Leuven, Belgium.

出版信息

J Neuroimmunol. 1995 Jun;59(1-2):77-82. doi: 10.1016/0165-5728(95)00027-y.

DOI:10.1016/0165-5728(95)00027-y

PMID:7797622

Abstract

The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR beta 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR beta 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB11501 allele and through linkage also of the DRB11501-DQA10102 haplotype with MS. In addition, the results showed that the DRB11501/DRB1*0400 or DR beta 1Ala71+ His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1Phe47+, DR beta 1Asp70+ and DR beta 1Thr140+, DQ alpha 1Phe25+, DQ alpha 1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)-DQ alpha 1Phe25+ and DR beta 1(Ser13+)-DQ alpha 1Phe25+ haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.

摘要

一些人类白细胞抗原（HLA）II类等位基因与多发性硬化症（MS）的关联已有大量文献记载。在本研究中，我们对78名无亲缘关系的白种人慢性进展型MS（CP MS）患者和204名对照者进行了研究，探讨了HLA II类单倍型和基因型以及位于DRβ1链抗原结合槽和CD4结合域的DRβ1位点多态性氨基酸的作用。结果证实了DRB11501等位基因以及通过连锁分析的DRB11501 - DQA10102单倍型与MS呈正相关。此外，结果表明DRB11501/DRB1*0400或DRβ1 Ala71 + His13 +基因型赋予MS最高的相对风险（RR = 9.14）。编码DRβ1 Phe47 +、DRβ1 Asp70 +和DRβ1 Thr140 +、DQα1 Phe25 +、DQα1 Leu69 +残基的等位基因具有保护作用，而DRβ1(Phe47 +)-DQα1 Phe25 +和DRβ1(Ser13 +)-DQα1 Phe25 +单倍型提供了最高的保护作用（RR = 0.24）。我们的结果表明，DQ和DRαβ异二聚体可能通过其抗原结合槽的形状，对患MS风险的增加或降低都有影响。