Actigraphic characterization of sleep and circadian phenotypes of PER3 gene VNTR genotypes

ABSTRACT

The molecular circadian timing system involves genes known as “clock genes,” such as the PER3 gene. Studies have demonstrated associations among a repeat polymorphism (VNTR) of the PER3 gene with chronotypes, with the occurrence of circadian rhythm disorders and with sleep homeostasis phenotypes. The aim of this study was to investigate, by actigraphy, sleep and circadian rhythm profiles of people with different genotypes for the VNTR polymorphism of the PER3 gene. We genotyped 467 individuals (46,39% male) for the PER3 VNTR polymorphism. The mean age of the participants was 21.84 $\pm$ 2.64, ranging from 18 to 30 y old. Actigraphy data were collected from a subsample of 81 subjects with PER3 4-repeats homozygous (PER3^4/4) or 5-repeats homozygous (PER3^5/5) genotypes from April to June of 2021. From this sample, 48 PER3^4/4 and 33 PER3^5/5 subjects wore a wrist actigraph between 12 and 19 d. The sleep onset (weekdays, p = 0.015; weekend, p = 0.022) and offset (weekdays, p = 0.004; weekend, p = 0.041) of the PER3^5/5 group occurred later than the PER3^4/4 group. Similar results were observed for the mid-sleep phase of weekdays (MSW) (p = 0.008) and free days (MSF) (p = 0.019), and for the mid-sleep phase corrected for sleep debt accumulated over the week (MSFsc) (p = 0.024). Despite the phase differences found between the PER3^4/4 and PER3^5/5 groups, no differences were found in sleep duration and social jet lag. However, the PER3^4/4 group presented, on average, a longer sleep rebound on the days off when compared to the PER3^5/5 (p = 0.002). The PER3^5/5 group showed lower interdaily stability (IS) (p = 0.032) and higher daily activity rhythm variability (IV) (p = 0.035). The findings of the present study revealed associations between the PER3 gene, sleep, and circadian rhythms. In general, we found that the gene is associated with the expression of sleep timing and duration and to the phase of the activity rhythm. The experiments carried out here occurred in the COVID-19 pandemic scenario, which should be considered as an environmental element with potential effects on the results obtained.

KEYWORDS:

• PER3 gene
• actigraphy
• sleep
• motor activity

Acknowledgments

We are grateful to the participants for their time and commitment.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by The São Paulo Research Foundation (FAPESP), grants [2019/06294-2 and 2014/50457-0].