EXTENSIVE HLA CLASS-II STUDIES IN 58 NON-DRB1-ASTERISK-15 (DR2) NARCOLEPTIC PATIENTS WITH CATAPLEXY

Narcolepsy is a sleep disorder that has been shown to be tightly assoc iated with HLA DR15 (DR2). In this study, 58 non-DR15 patients with na rcolepsy-cataplexy were typed at the HLA DRB1, DQA1 and DQB1 loci. Sub jects included both sporadic cases and narcoleptic probands from multi plex families. Additional markers studied in the class II region were the promoters of the DQA1 and DQB1 genes, two CA repeat polymorphisms (DQCAR and DQCARII) located between the DQA1 and DQB 1 genes, three CA repeat markers (G51152, T16CAR and G411624R) located between DQB 1 an d DQB3 and polymorphisms at the DQB2 locus. Twenty-one (36%) of these 58 non-DR15 narcoleptic patients were DQA10102 and DQB1*0602, a DQ1 s ubtype normally associated with DRB115 in DR2-positive narcoleptic su bjects. Additional microsatellite and DQA1 promoter diversity was foun d in some of these non-DR15 but DQB10602-positive haplotypes but the known allele specific codons of DQA10102 and DQB1*0602 were maintaine d in all 21 cases. The 37 non-DQA10102/DQB1*0602 subjects did not sha re any particular HLA DR or DQ alleles. We conclude that HLA DQA10102 and DQB10602 are the most likely primary candidate susceptibility ge nes for narcolepsy in the HLA class II region.