HLA and hypocretin studies in Korean patients with narcolepsy

STUDY OBJECTIVES: Very few studies have evaluated narcolepsy in Asian countries, outside of Japan. Our goal was to study narcolepsy at the genetic, clinical and pathophysiological level in Korea. DESIGN: Prospective study of consecutive patients and age matched controls. Clinical data ascertained from the Stanford Sleep Inventory, Polysomnography and MSLT data, as well as clinical notes. High resolution DRB1 and DQB1 typing in all subjects and studies of CSF hypocretin-1 was also evaluated in a subset of patients. PARTICIPANTS AND SETTING: 20 patients diagnosed at St. Vincent and Korea University Hospitals (Seoul, Korea). 21 Korean control subjects. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: For narcoleptic subjects, mean age was 28.2 years old and 45% were female. Mean BMI was 23.9+/-3.4 kg/m2, a significantly higher value than that expected in an age- and sex-matched sample (p<0.01). All patients had sleepiness and cataplexy while the prevalence of other symptoms ranged from 60-75%. All but 2 subjects were HLA-DR15 (DR2), DQB1*0602 positive (90%). This high DQB1*0602 percentage compared with 24% DQB1*0602 positivity in 21 control Koreans. Protective effects were observed for the DQB1*0601 and DRB1*0406 alleles, Hypocretin (orexin) CSF studies were also performed in 6 cataplectic subjects, all of which had undetectable CSF hypocretin levels. Two of these subjects had started narcolepsy less than 1 year before analysis yet had undetectable hypocretin levels. CONCLUSION: These results illustrate the similarity of narcolepsy-cataplexy in Korea in comparisons with other more studied populations. We also identified a new potential HLA protective subtype, HLA-DRB1*0406.