Hillert J, Olerup O
Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
Neurology. 1993 Jan;43(1):163-8. doi: 10.1212/wnl.43.1_part_1.163.
The HLA class II haplotype DR15,DQ6,Dw2 is associated with an increased risk for multiple sclerosis (MS). It has previously been shown that this haplotype extends to the HLA-DQA2 locus but not to the HLA-DP subregion. We report the distribution in 148 MS patients and 158 healthy controls of Taq I restriction fragments of the C4, cytochrome P-21 (CYP21), and HLA-B genes. Approximately 90% of the DR15,DQ6,Dw2 haplotypes extend to the C4/CYP21 loci and 50% to the HLA-B locus, indicated by a significant association of the haplotype with restriction fragments of these loci. However, there was no independent association in MS patients with these genes. This indicates that the susceptibility to MS is coded for by genes within or close to the HLA-DR-DQ subregion. Furthermore, the delineation of the DR15,DQ6,Dw2 haplotype is very similar in MS patients and control subjects. This observation supports the hypothesis that "normal" genes, common to all carriers of the DR15,DQ6,Dw2 haplotype, confer the increased genetic susceptibility to MS associated with this haplotype.
人类白细胞抗原（HLA）II类单倍型DR15、DQ6、Dw2与多发性硬化症（MS）风险增加相关。此前已表明，该单倍型延伸至HLA - DQA2基因座，但未延伸至HLA - DP亚区域。我们报告了148例MS患者和158例健康对照中C4、细胞色素P - 21（CYP21）和HLA - B基因的Taq I限制性片段分布情况。约90%的DR15、DQ6、Dw2单倍型延伸至C4/CYP21基因座，50%延伸至HLA - B基因座，这由该单倍型与这些基因座的限制性片段显著相关表明。然而，在MS患者中这些基因不存在独立关联。这表明MS易感性由HLA - DR - DQ亚区域内或附近的基因编码。此外，DR15、DQ6、Dw2单倍型在MS患者和对照受试者中的界定非常相似。这一观察结果支持了以下假设：DR15、DQ6、Dw2单倍型所有携带者共有的“正常”基因赋予了与该单倍型相关的MS遗传易感性增加。
