Danyella Silva Pereira

Clock polymorphisms and circadian rhythms phenotypes in a sample of the Brazilian population

A Clock polymorphism T to C situated in the 3′ untranslated region (3′‐UTR) has been associated with human diurnal preference. At first, Clock 3111C had been reported as a marker for evening preference. However these data are controversial, and data both corroborating and denying them have been reported. This study hypothesizes that differences in Clock genotypes could be observed if extreme morning‐type subjects were compared with extreme evening‐type subjects, and the T3111C and T257G polymorphisms were studied. The possible relationship between both polymorphisms and delayed sleep phase syndrome (DSPS) was also investigated. An interesting and almost complete linkage disequilibrium between the polymorphisms T257G in the 5′ UTR region and the T3111C in the 3′ UTR region of the Clock gene is described. Almost always, a G in position 257 corresponds to a C in position 3111, and a T in position 257 corresponds to a T in position 3111. The possibility of an interaction of these two regions in the Clock messenger RNA structure that could affect gene expression was analyzed using computer software. The analyses did not reveal an interaction between those two regions, and it is unlikely that this full allele correspondence affects Clock gene expression. These results show that there is no association between either polymorphism T3111C or T257G in the Clock gene with diurnal preference or delayed sleep phase syndrome (DSPS). These controversial data could result from the possible effects of latitude and clock genes interaction on circadian phenotypes.

Detecting chronotype differences associated to latitude: a comparison between Horne--Östberg and Munich Chronotype questionnaires.

Abstract Background: Chronotype, phase preference to perform activities during a 24-hour day, represents distinct circadian temporal organization of living organisms. Morning and evening types can be identified by questionnaires such as Horne and Östberg (HO) and Munich Chronotype Questionnaire (MCTQ). Environmental factors, such as different light–dark cycles experienced at different latitudes, interact with the organisms’ circadian timekeeping system. Therefore, chronotype is expected to vary as a result of different geographical locations. Aim: To identify differences in chronotype distribution in populations of two Brazilian cities, Natal and Sao Paulo, located at different latitudes. Subjects and methods: Two specific questionnaires, the Horne and Östberg Questionnaire (HO) and the Munich Chronotype Questionnaire (MCTQ), were used to identify chronotypes of undergraduate students from São Paulo and Natal. Results: The comparison of the curve distributions of HO and MCTQ scores between both cities allowed one to observe that, while HO curves of São Paulo and Natal overlapped, MCTQ curves showed a clear shift towards eveningness in São Paulo. Conclusion: This experiment confirmed results from previous studies that the farther away from the equator, the longer the delay of the sleep phase. It was also concluded that MCTQ is better at detecting this phenomenon.

Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans.

Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology.

Erratum to “Screening for polymorphisms in the AANAT gene and their association with extreme diurnal preference” [Sleep Sci. 6 (4) (2013) 141–145

In the article “Screening for polymorphisms in the AANAT gene and their association with extreme diurnal preference” by Bruna Del Vechio Koike, Danyella Silva Pereira, Sergio Tufik and Mario Pedrazzoli, which appeared on pages 141–145 of the December 6, 2013 issue 4. The legend in Fig. 2 contained a misprint. The label of the first (left) column was missing one polymorphism. Instead GATAA, the correct is GACTAA. The letter “C” was not there. Another mistake is concerned about Table 3. The last polymorphism was included in the analysis and the correct allele is A, not C. Therefore, all the haplotypes in that table ends with the A allele in the last polymorphisms. So, the haplotypes in the table are: GACTAA, CACTAA, CACAAA, CGCTAA e GACAAA as showed in Fig. 2. Fig. 2 Table 3