Association Study of a Variable-Number Tandem Repeat Polymorphism in the Clock Gene PERIOD3 and Chronotype in Norwegian University Students

Abstract

Circadian rhythms are endogenously generated cycles involving physiological parameters, such as core body temperature, hormone levels, blood pressure, sleep, and metabolism, with a period length of around 24 h. The circadian clock in mammals is regulated by a set of clock genes that are functionally linked together, and polymorphisms in clock genes could be associated with differences in circadian rhythms. A variable-number tandem repeat (VNTR) in the human clock gene PERIOD3 (PER3) has been suggested to correlate with a morning (lark) versus evening (owl) chronotype as well as with the circadian rhythm sleep disorder “delayed sleep phase disorder” (DSPD). The authors examined 432 healthy Norwegian university students in search of further support for an association between the PER3 polymorphism and diurnal preference. The Horne-Östberg Morningness-Eveningness Questionnaire (MEQ) and Preferences Scale (PS) were used to evaluate subjective chronotype. DNA samples were genotyped with respect to the 4-repeat and 5-repeat alleles of the VNTR PER3 polymorphism, and the genotype distribution was 192 (4-4), 191 (4-5), and 49 (5-5). The authors estimated that the power to detect an association of the 4-allele with preference for morningness or eveningness was 75%. The authors found no association between the PER3 clock gene and chronotype, indicating that the proposed role of PER3 needs further clarification. (Author correspondence: [email protected])

Keywords:

• Association study
• Chronotype
• Circadian rhythm
• Diurnal preference
• Genotype
• Morningness/eveningness
• PER3

ACKNOWLEDGMENTS

We thank the study participants and we are grateful to Torill Johansen, Tom Halvor Lilleholt, and Idalill Udnes for help in collecting the saliva samples and administering the questionnaires. We also thank Marit Næsse at HUNT Biosciences for assistance with DNA purification and quality control of the samples. This study was supported by the Research Council of Norway, Helse Vest RHF and Dr. Einar Martens Fund.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.