A search for a mutation associated with narcolepsy.

发作性睡病与HLA DR 2（DR 15）抗原几乎100%相关的显著证据是阐明这种睡眠障碍的分子基础的重要线索。肿瘤坏死因子α（TNF α）的基因位于HLA II类基因簇中。最近的研究表明，TNF α在正常人类睡眠的调节中起着重要作用，并且这种细胞因子的调节在发作性睡病中可能被扰乱。我们通过单链构象多态性（SSCP）分析寻找与发作性睡病相关的TNF α基因突变。在两种不同的实验条件下，对12个300- 500 bp的PCR片段进行了两次检测，所述PCR片段覆盖启动子区、外显子和内含子。在发作性睡病患者TNF α基因启动子区发现了一种新的多态性，C-850 T。用限制性片段长度多态性方法检测基因型频率。92例发作性睡病患者和91例正常对照者的基因型分布差异无统计学意义。这些结果并不支持我们的假设，TNF α产生的遗传异常是发病性嗜睡症。

The striking evidence of almost 100% association of narcolepsy with HLA DR2(DR15) antigen is an important clue to elucidate molecular basis of this sleep disorder. The gene for tumor necrosis factor alpha (TNF alpha) is located in the HLA class II gene cluster. Recent studies have indicated that TNF alpha plays an important role in regulation of normal human sleep and regulation of this cytokine may be disturbed in narcolepsy. We searched for a mutation associated with narcolepsy in the TNF alpha gene by single-strand conformation polymorphism (SSCP) analysis. Twelve PCR fragments of 300-500bp covering promoter region, exons, and introns, are examined twice at two different experimental conditions. A novel polymorphism, C-850T, was found in the promoter region of the TNF alpha gene in narcoleptic patients. Genotype frequency was examined by restriction fragment length polymorphism method. No significant difference of genotype distribution was found between 92 patients with narcolepsy and 91 normal controls. These results do not support our hypothesis that genetic abnormality of TNF alpha production is pathogenetic for narcolepsy.