HLA DQB1-ASTERISK-0602 IS ASSOCIATED WITH CATAPLEXY IN 509 NARCOLEPTIC PATIENTS

Narcolepsy is a sleep disorder associated with HLA DR15 (DR2?) and DQB 10602.? We HLA typed 509 patients enrolled in a clinical trial for th e drug modafinil and analyzed the results in relation to cataplexy, a symptom of narcolepsy characterized by muscle weakness triggered by em otions. The patients were tither subjects with cataplexy who had a mea n sleep latency (SL) of less than 8 minutes and two or more sleep onse t rapid eye movement (REM) periods (SOREMPs) during a multiple sleep l atency test, or narcoleptic patients without cataplexy but with a mean SL shorter than 5 minutes and two or more SOREMPs. The respective val ues of DRB115 (DR2) and DQB1*0602 as markers for narcolepsy were firs t compared in different ethnic groups and in patients with and without cataplexy. DQB10602 was found to be a more sensitive marker for narc olepsy than DRB115 across all ethnic groups. DBQ1*0602 frequency was strikingly higher in patients with cataplexy versus patients without c ataplexy (76.1% in 421 patients versus 40.9% in XX patients). Positivi ty was highest in patients with severe cataplexy (94.8%) and progressi vely decreased to 54.2% in patients with the mildest cataplexy. A volu ntary 50-item questionnaire focusing on cataplexy was also analyzed in 212 of the 509 HLA-typed patients. Subjects with definite cataplexy a s observed by an experienced clinician were more frequently HLA DQB10 602-positive than those with doubtful cataplexy, and the manifestation s of cataplexy were clinically more typical in DQB10602-positive pati ents. These results show that the HLA association is!, as tight as pre viously reported (85-95%) when cataplexy is clinically ;typical or sev ere. We also found that patients with mild. atypical, or no cataplexy have a significantly increased DQB10602 frequency (40-60%) in compari son with ethnically matched controls (24%). These results could be exp lained bq; increased disease heterogeneity in the noncataplexy group o r by a direct. effect of the HLA DQB1-0602 genotype on the clinical ex pression of narcolepsy.