Novel polymorphism in the promoter region of the tumor necrosis factor alpha gene: No association with narcolepsy.

The striking evidence of almost 100% association of narcolepsy with human leukocyte antigens (HLA) DR2(DR15) antigen is an important clue to elucidate the 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 the 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 promoter region of the TNF alpha gene by single-strand conformation polymorphism analysis. A novel polymorphism, C-850T, was found 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.