Triplet repeat polymorphism within the NOTCH4 gene located near the junction of the HLA class II and class III regions in narcolepsy.

A polymorphic (CTG)n microsatellite repeat was found in the signal peptide domain of the NOTCH4 gene located near the junction of the class II and class III regions of the human major histocompatibility complex. This gene belongs to a multigene family of NOTCH originally identified as a differential factor of neuronal cells. To ascertain whether the NOTCH4 gene is involved in the development of neurogenic disease, narcolepsy, which is known to be tightly associated with HLA-DR15, this microsatellite polymorphism of the (CTG)n repeat was analyzed in Japanese patients with narcolepsy One allele, 9 repetitions of CTG (Leu) was significantly increased in the patient group. However, the significant increase of this allele in the patient group could be explained by a strong linkage disequilibrium with the HLA class II alleles, DRB1*1501, DQA1*0102 and DQB1*0602, which were more strongly associated with the disease. These results suggest that the (CTG)n repeat polymorphism in NOTCH4 does not primarily determine the susceptibility to narcolepsy.