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 p eptide domain of the NOTCH4 gene located near the junction of the clas s II and class III regions of the human major histocompatibility compl ex. This gene belongs to a multigene family of NOTCH originally identi fied 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, thi s microsatellite polymorphism of the (CTG)(n) repeat was analyzed in J apanese patients with narcolepsy. One allele, 9 repetitions of CTG (Le u) was significantly increased in the patient group. However, the sign ificant increase of this allele in the patient group could be explaine d by a strong linkage disequilibrium with the HLA class II alleles, DR B11501, DQA1*0102 and DQB1*0602, which were more strongly associated with the disease. These results suggest that the (CTG)(n) repeat polym orphism in NOTCH4 does not primarily determine the susceptibility to n arcolepsy.