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 l eukocyte antigens (HLA) DR2(DR15) antigen is an important clue to elucidate the molecular basis of this sleep disorder. The gene for tumor necrosis fa ctor 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 regula tion of normal human sleep, and regulation of this cytokine may be disturbe d in narcolepsy. We searched for a mutation associated with narcolepsy in t he promoter region of the TNF alpha gene by single-strand conformation poly morphism analysis, A novel polymorphism, C-850T, was found in narcoleptic p atients. Genotype frequency was examined by restriction fragment length pol ymorphism method. No significant difference of genotype distribution was fo und between 92 patients with narcolepsy and 91 normal controls. These resul ts do not support our hypothesis that genetic abnormality of TNF alpha prod uction is pathogenetic for narcolepsy, Am. J, Med, Genet, (Neuropsychiatr. Genet.) 88:301-304, 1999, (C) 1999 Wiley-Liss, Inc.