Narcolepsy genetic marker HLA DQB1*06:02 and excessive daytime sleepiness in Parkinson disease patients treated with dopaminergic agents

Abstract

To determine whether narcolepsy Human Leukocyte Antigen (HLA) risk allele DQB1*0602 is associated with excessive daytime sleepiness (EDS) and inappropriate sleep in patients with Parkinson disease (PD). EDS is a common and disabling non-motor manifestation of PD, affecting quality of life and driving performance. DQB1*0602 is an HLA risk allele for narcolepsy. It is present in 12–30% of the general population. We hypothesize that DQB1*0602 is associated with an increased risk of EDS and inappropriate sleep in PD patients. This was a cross-sectional observational study of 150 PD individuals on dopaminergic agents. Main outcome measures were DQB1*0602 status and the modified Epworth Sleepiness Scale. Individuals with dementia, loss of independence, narcolepsy and untreated sleep apnea were excluded. Confounding variables for EDS were assessed using Parkinson Disease Sleep Scale, Mayo Sleep Questionnaire, Unified PD Rating Scale, Hoehn and Yahr scale. DQB1*06:02 positive PD patients were approximately three times more likely to experience EDS and fall asleep inappropriately during activities that required sustained alertness (e.g. driving, eating, attending work etc.). Exploratory post hoc analysis showed a dopaminergic drug dose- and type- dependent effect on daytime sleepiness in DQB1*06:02 positive individuals. No significant differences were found in confounding variables. PD individuals are more likely to experience EDS and fall asleep inappropriately during activities if DQB1*0602 positive. Genetic vulnerability may explain EDS risk in PD.