Wilner A, Steinman L, Lavie P, Peled R, Friedmann A, Brautbar C
Department of Genetics, Hebrew University, Jerusalem, Israel.
Hum Immunol. 1988 Jan;21(1):15-22. doi: 10.1016/0198-8859(88)90077-8.
Narcolepsy is a very rare disease among Israeli Jews with a frequency of 7/3 X 10(6). An investigation of the association of narcolepsy with the human leukocyte antigen system was conducted in Israeli Jews at the serologic and genomic levels. The human leukocyte antigen class I and class II antigen typing of 7 clinically diagnosed narcoleptics, 3 individuals suffering from sleep disorders other than narcolepsy, and 11 healthy matched controls revealed that all narcoleptic patients (100%) investigated in the present study carried the HLA-DR2 haplotype, whereas patients with other sleep disorders did not. The HLA-B7 and DR2 occurred jointly in 57% (4/7) of the narcoleptic patients, as compared to 2% in randomly selected Israeli healthy controls. Restriction fragment length polymorphism analysis was performed with several restriction enzymes and three cDNA probes for DQ alpha, DQ beta, and DR beta genes on genomic DNAs obtained from narcoleptics and patients with other sleep disorders, matched controls, and 3 homozygous typing cells representing the DR2 subtypes Dw2, Dw12, and DwAZH. The restriction fragment length polymorphism analysis showed that all narcoleptics (7 of 7) shared virtually identical restriction fragment length polymorphisms with one of the homozygous typing cells (GSO), which defines DR2,Dw2. The frequency of the DR2,Dw2 haplotype in the healthy Israeli population is 3.2%. Other non-narcoleptic patients did not share these restriction fragment length polymorphisms. These findings indicate that narcolepsy is associated worldwide with the HLA-DR2,Dw2 haplotype.
发作性睡病在以色列犹太人中是一种非常罕见的疾病，发病率为7/3×10⁶。在以色列犹太人中，针对发作性睡病与人类白细胞抗原系统的关联在血清学和基因组水平上进行了调查。对7名临床诊断为发作性睡病的患者、3名患有除发作性睡病外其他睡眠障碍的个体以及11名健康匹配对照进行人类白细胞抗原I类和II类抗原分型，结果显示本研究中所有接受调查的发作性睡病患者（100%）携带HLA - DR2单倍型，而患有其他睡眠障碍的患者则没有。HLA - B7和DR2在57%（4/7）的发作性睡病患者中共同出现，相比之下，在随机选择的以色列健康对照中这一比例为2%。使用几种限制性内切酶以及针对DQα、DQβ和DRβ基因的三种cDNA探针，对从发作性睡病患者、患有其他睡眠障碍的患者、匹配对照以及代表DR2亚型Dw2、Dw12和DwAZH的3个纯合分型细胞获得的基因组DNA进行限制性片段长度多态性分析。限制性片段长度多态性分析表明，所有发作性睡病患者（7例中的7例）与定义DR2、Dw2的一个纯合分型细胞（GSO）几乎共享相同的限制性片段长度多态性。DR2、Dw2单倍型在以色列健康人群中的频率为3.2%。其他非发作性睡病患者不共享这些限制性片段长度多态性。这些发现表明，在全球范围内发作性睡病与HLA - DR2、Dw2单倍型相关。
