Human period-3 gene involvement in diurnal preference among Argentinean bipolar disorders patients

CASIRAGHI L.P., MARTINO D.J., MARENGO E., IGOA A., AIS E.D., STREJILEVICH S.A., GOLOMBEK D.A.

Sleep Science

Associação Brasileira de Sono - Sleep Science

Lugar: San Pablo; Año: 2010 vol. 3 p. 22 - 26

1984-0659

Background and objective: Due to circadian disturbances observed among bipolar disorder (BD) patients, several studies have analyzed a posible link with genes involved in the molecula generation of biological rhythms. Some of these genes have been previously associated with diurnal preference (i.e. chronotype) in healthy individuals. In this study, we aimed to establish the influence of two genetic polymorphisms on chrnotypes among two local populations of healthy subjects and individuals affected for bipolar disorders. Methods: The polymorphisms analyzed were a variable number of tandem repeats (4 or 5-repeat alleles; 4R or 5R) in exon 18 of hper3, and T/C single nucleotide polymorphism in clock. Chronotype of healthy individuals (n=39) and patients were determined by the Home and Ostberg Questionnaire, and the control populations was divided in three groups according to results. Results: No difference in allele or genotype frequencies was detected between control and bipolar disorder populations. In controls, the 5R allele in hper3 and the C allele in clock were sub-represented among evening-type individuals (p<0.005). Moreover, subjects homozigous for the 4R allele of hper3 had significantly lower scores (evening preference) than 5R allele carries among both controls (p<0.005) and patients (p<0.001). Conclusions: We have confirmed the strong correlation of hper3 variable number of tandem repeats (VNTR) polymorphism with diurnal preference on a local population, even when not taking into account the chronotype classification. This correlation was replicated with an even strongest robustness, on patients with bipolar disorders. These findings add to the growing body of evidence supporting an important role for hper3 on human circadian physiology.