Tanaka Susumu, Honda Yutaka, Honda Makoto
Sleep Disorders Project, Department of Sleep Disorders Research, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan.
Sleep. 2008 May;31(5):749-51. doi: 10.1093/sleep/31.5.749.
There is a close association between narcolepsy and the human leukocyte antigen (HLA)-DQB1*0602. The detailed influence and function of this specific HLA allele with regard to narcolepsy have not yet been elucidated. Our previous report identified the myxovirus resistance 2 (MX2) gene as a narcolepsy-specific dysregulated gene; however, the report had a limitation-the control groups were not HLA matched. In this study, we examined the possibility of an association between MX2 expression and HLA haplotypes.
The expression levels of the MX2 gene in 3 groups (24 narcolepsy with cataplexy patients; 24 age-, sex-, and HLA-DQB1 genotype-matched controls; and 24 age- and sex-matched controls without the HLA-DQB1*0602 allele) were measured by quantitative real-time RT-PCR.
The expression level of the MX2 gene tended to be downregulated in subjects carrying HLA-DQB1*0602, compared with that of the control subjects without this allele. There was no difference in the MX2 expression level between the narcolepsy subjects and the HLA-DQB1 genotype-matched control subjects.
Our previous finding-the narcolepsy-specific reduction of MX2 gene expression-was not replicated in this follow-up study. The expression level of the MX2 gene in white blood cells was found to be lower in subjects with the HLA-DQB10602 than in subjects without this allele, suggesting that there exists a relationship between the HLA-DQB10602 allele and MX2 gene expression. This might be a possible explanation for the strong HLA association observed in narcolepsy.
发作性睡病与人类白细胞抗原（HLA）-DQB1*0602密切相关。该特定HLA等位基因对发作性睡病的具体影响和功能尚未阐明。我们之前的报告将抗黏液病毒2（MX2）基因鉴定为发作性睡病特异性失调基因；然而，该报告存在一个局限性——对照组未进行HLA匹配。在本研究中，我们探讨了MX2表达与HLA单倍型之间关联的可能性。
通过定量实时RT-PCR检测3组人群（24例伴猝倒的发作性睡病患者；24例年龄、性别和HLA-DQB1基因型匹配的对照；以及24例年龄和性别匹配但无HLA-DQB1*0602等位基因的对照）中MX2基因的表达水平。
与无该等位基因的对照受试者相比，携带HLA-DQB1*0602的受试者中MX2基因的表达水平有下调趋势。发作性睡病受试者与HLA-DQB1基因型匹配的对照受试者之间的MX2表达水平无差异。
我们之前的发现——发作性睡病特异性的MX2基因表达降低——在本后续研究中未得到重复。发现携带HLA-DQB10602的受试者白细胞中MX2基因的表达水平低于无该等位基因的受试者，提示HLA-DQB10602等位基因与MX2基因表达之间存在关联。这可能是发作性睡病中观察到的HLA强关联的一种可能解释。
