Human period-3 gene is involved in diurnal preference in an Argentinean population of bipolar disorders patients.

CASIRAGHI, L; MARTINO, D; MARENGO, E; IGOA, A; AIS, E; STREJILEVICH, S; GOLOMBEK, DA

Sleep Science Journal

Associação Brasileira de Sono

Año: 2010 vol. 3 p. 22 - 26

1984-0659

Objective: Due to circadian disturbances observed among bipolar disorders (BDs) patients, several studies have analyzed a possible link with genes involved in the molecular generation of biological rhythms. Some of these genes have been previously associated to diurnal preference (i.e., chronotype) in healthy individuals. In this study we aimed to establish the influence of two genetic polymorphisms on chronotypes within two local populations of healthy subjects and individuals affected with BDs. Methods: The polymorphisms analyzed were a variable number of tandem repeats (4 or 5 repeats-alleles; 4R or 5R) in exon 18 of hper3, and a T/C single nucleotide polymorphism in clock. Chronotypes of healthy individuals (n=39) and patients (n=37) were determined by the Horne-Ostberg Questionnaire, and the control population was divided into three groups according to results. Results: No difference in allele or genotype frequencies was detected between control and BDs populations. In controls, the 5R allele in hper3 and the C allele in clock were sub-represented among evening-type individuals (p<0.05). Moreover, subjects homozygous for the 4R allele of hper3 had significatively lower scores (evening preference) than 5R allele-carriers among both controls (p<0.05) and patients (p<0.001). Conclusions: We have confirmed the strong correlation of hper3 VNTR polymorphism with diurnal preference on a local population, even when not taking into account chronotype classification. This correlation was replicated, with an even stronger robustness, on BDs patients. These findings add to the growing body of evidence supporting an important role for hper3 on human circadian physiology.