Phenotypic characterization of circadian rhythms, sleep, and Body Mass Index (BMI) in undergraduate students with different genotypes for the VNTR polymorphism in the PER3 gene

Author(s)

Juliana Viana Mendes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Artes, Ciências e Humanidades (EACH)
• Defense date: 2022-09-16

Examining board members

Mario Pedrazzoli Neto; Bruno Jacson Martynhak; Camilo Rodrigues Neto; Eduardo Henrique Rosa Santos

• Advisor: Mario Pedrazzoli Neto; Ana Amélia Benedito Silva

Abstract

Introduction: The molecular circadian system temporization involves genes known as clock genes, such as the PER3 gene. These genes are associated with the regulation of processes such as adaptation to the environmental light/dark cycle, the sleep/wake cycle, and the body temperature cycle. Studies demonstrate the association between a repeat polymorphism (VNTR) of the PER3 gene with chronotypes and with the occurrence of circadian rhythm disorders. Objective: To investigate the possible relationship between the sleep profile, the activity/rest rhythm profile, metabolism, and the VNTR repeat polymorphism of the PER3 gene. Material and methods: The study was carried out on an undergraduate sample from the School of Arts, Sciences and Humanities of the University of São Paulo in two stages: in the first stage, carried out in 2019, 513 students had saliva samples collected and all were genotyped (according to the three possible genotypes: PER34/4, PER34/5, and PER35/5) for the VNTR repeat polymorphism of the PER3 gene. At this stage, anthropometric and sleep habits data were collected via an online questionnaire; in the second stage, during the COVID-19 pandemic, anthropometry data and sleep and motor activity data were obtained from a subsample of 81 students, only of the PER34/4 and PER35/5 genotypes, who agreed to use wrist actigraphs. Results: In the first stage of the study, 467 individuals (91.03% of the initial sample) had their genotype identified: 196 were PER34/4, 212 were PER34/5 and 59 were PER35/5. In the second stage of the experiment, 48 PER34/4 subjects and 33 PER35/5 subjects used a wrist actigraph for, on average, 15 consecutive days. The sleep start and end times of the PER35/5 group occurred later than those of the PER34/4 group, the same occurring with the mid-sleep phase of study days (MSW) and days off (MSF), and with the mid-sleep phase corrected for sleep debt accumulated over the week (MSFsc). Despite the phase differences found between the PER34/4 and PER35/5 groups, no differences were found in sleep duration and social jetlag. However, the PER34/4 group presented, on average, greater sleep rebound when compared to the PER35/5. The PER35/5 group showed lower interdaily stability (IS) and greater fragmentation (IV) of the activity/rest rhythm than the PER34/4 group. There was no association between BMI variation over time (BMI) and sleep variables. A statistically significant correlation was observed between BMI and interdaily stability (IS) (r=-0.279; p=0.027) considering all individuals; only in the PER34/4 group, a significant correlation was found between BMI and intraday variability (IV) (r=0.375; p=0.022). Conclusion: The findings of the present study show that there are associations between the PER3 gene, sleep, circadian rhythms, and aspects of metabolism. In general, we found that the gene is linked to the expression of sleep schedules and the phase of the activity/rest rhythm and that there is also a genetic mediation of aspects of metabolism linked to BMI, due to a rhythmic disruption. The experiments carried out here were based on the COVID-19 pandemic scenario, which should be considered as an environmental element with active potential in the results obtained (AU)

• FAPESP's process: 19/06294-2 - Phenotypic characterization of circadian rhythms and body mass index (BMI) in individuals with different genotypes for clock genes polymorphisms: comparison between college students from morning and evening schedules
• Grantee: Juliana Viana Mendes
• Support Opportunities: Scholarships in Brazil - Master