Sequence variants in circadian rhythmic genes in a cohort of patients suffering from hypersomnia of central origin

Abstract

The mutation analysis of circadian genes in different sleep disorders revealed only a few disease-causing mutations so far. Cryptochrome 1 + 2 (CRY1, CRY2) and aryl hydrocarbon receptor nuclear translocator-like (ARNTL also known as BMAL1) are genes that play a major role in the adherence to circadian rhythm. Excessive daytime sleepiness (EDS) presents as the dissociation from the circadian rhythm and is the leading symptom of sleep disorders, which are summarised as hypersomnias of central origin. We performed an association studies in 86 German Caucasian patients suffering from EDS to analyze whether there is a genetic predisposition resulting from the involvement of sequence variants in the genes CRY1, CRY2 and ARNTL. One polymorphism in CRY1 was detected, which was associated with EDS regardless of the underlying specific sleep disorder. The result suggests that CRY1 could play a possible role in the complex genetics of hypersomnias of central origin.

Keywords:

• hypersomnia
• narcolepsy
• EDS
• polymorphisms
• CRY
• ARNTL

Acknowledgements

Svenja Happe received honoraries from UCB Schwarz Pharma, Cephalon, Boehringer Ingelheim, Pfizer, Hoffmann La Roche, Janssen Cilag and Sanofi Aventis. Peter Young received honoraries from UCB Schwarz Pharma, Cephalon, Boehringer Ingelheim and Sanofi Aventis. Geert Mayer received honoraries from UCB Schwarz Pharma, Cephalon, Janssen Cilag, Pfizer, Glaxo Smith-Kline and Sanofi Aventis.