ASSOCIATION OF A SINGLE NUCLEOTIDE POLYMORPHISM IN TNFA PROMOTOR REGION WITH NARCOLEPSY.
H Hohjoh, T Nakayama, J Ohashi, T Miyagawa, M Kawashima, H Tanaka, T Akaza, Y Honda, T Juji and K Tokunaga, Dept. of Human Genetics, Univ. of Tokyo, Japanese Red Cross Central Blood Center, and Seiwa Hosp. Neuropsychiatric Res. Inst., Tokyo, Japan.

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Narcolepsy is a sleep disorder in which multiple factors including environmental and genetic factors are involved. A particular HLA class II haplotype, DRB1*1501-DQB1*0602, is known to be strongly associated with the disorder. Tumor necrosis factor-alpha (TNFA) is a cytokine with multiple functions: it participates not only in immune response but also in sleep as a sleep-promoting substance. In the present study, we performed an association study between five known single-nucleotide polymorphisms (SNPs) in the promoter region of TNFA gene located in the class III region and human narcolepsy. The results indicated that the frequency of -857T was significantly increased in the patients as compared with that in the controls: chi-square = 8.85, P = 0.0029. In addition, presumed haplotypes with HLA-DRB1, -857 SNP, and HLA-B loci suggested that -857 T is mainly associated with DRB1 alleles other than DRB1*1501, thus the significant increase of -857 T in the patients may not caused by the association with DRB1*1501. Therefore, it is conceivable that the TNFA with -857 T is associated with narcolepsy independently of the established association of DRB1*1501.