The impact of PER3 VNTR polymorphism on the development of schizophrenia in a Turkish population

Ozsoy F., YIgIt S., Nursal A.F., Kulu M., Karakus N.

Up to 80 % of patients who suffer from schizophrenia have sleep impairments, which affect physical and mental health, as well as quality of life. Several tandem repeat polymorphisms (VNTRs) in the Period 3 (Per3) gene have been associated with heritable sleep and circadian variables. The purpose of this study is to investigate the relationship between the VNTR variant of the PER3 gene and genetic predisposition of schizophrenia in a Turkish population. Blood samples were taken from 100 patients with schizophrenia, and from 100 normal controls who are age and sex­matched. PER3 genotyping was performed on DNA by polymerase chain reaction (PCR) using specific primers. For the PER3 VNTR polymorphism, we found no significant differences in the genotype distribution and allele frequency, between the schizophrenia and control groups. No association was noted between clinical and demographical characteristics of schizophrenia patients and the PER3 VNTR genotype distribution. This is the first study investigating association of the PER3 VNTR polymorphism with schizophrenia in a Turkish population. In conclusion, the results of this study do not support an association between the PER3 VNTR polymorphism and risk of schizophrenia in a Turkish population.

Key words: Schizophrenia, Period 3, gene, polymorphism, PCR, VNTR

Tsitologiya i Genetika 2021, vol. 55, no. 2, pp. 77-78

1. M.D., Specialist, Department of Psychiatry, Tokat State Hospital, Tokat, Turkey
2. Associate Professor, Department of Medical Biology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey
3. Department of Genetics, Faculty of Veterinary Medicine, Ondokuz Mayis University, Samsun, Turkey
4. Associate Professor, Department of Medical Genetics, Faculty of Medicine, Hitit University, Corum, Turkey
5. M.D., Specialist, Department of Psychiatry, Tokat Dr.Cevdet Aykan Mental Health and Diseases Hospital, Tokat, Turkey

E-mail: serbulent.yigit gmail.com

Ozsoy F., YIgIt S., Nursal A.F., Kulu M., Karakus N. The impact of PER3 VNTR polymorphism on the development of schizophrenia in a Turkish population, Tsitol Genet., 2021, vol. 55, no. 2, pp. 77-78.

In "Cytology and Genetics":
Filiz Ozsoy, Serbulent Yigit, Ayse Feyda Nursal, Muberra Kulu & Nevin Karakus The Impact of PER3 VNTR Polymorphism on the Development of Schizophrenia in a Turkish Population, Cytol Genet., 2021, vol. 55, no. 2, pp. 188–193
DOI: 10.3103/S0095452721020109

References

1. Afonso, P., Brissos, S., Figueira, M.L., et al., Schizophrenia patients with predominantly positive symptoms have more disturbed sleep–wake cycles measured by actigraphy, Psychiatry Res., 2011, vol. 189, no. 1, pp. 62–66. https://doi.org/10.1016/j.psychres.2010.12.031

2. Afonso, P., Figueira, M.L., and Paiva, T., Sleep-promoting action of the endogenous melatonin in schizophrenia compared to healthy controls, Int. J. Psychiatry Clin. Pract., 2011, vol. 15, no. 4, pp. 311– 315. https://doi.org/10.3109/13651501.2011.605954

3. An, H., Zhu, Z., Zhou, C., et al., Chronotype and a PERIOD3 variable number tandem repeat polymorphism in Han Chinese pilots, Int. J. Clin. Exp. Med., 2014, vol. 7, no. 10, pp. 3770–3776. https://doi.org/10.1371/journal.pone.0005874

4. Archer, S.N., Robilliard, D.L., Skene, D.J., et al., A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference, Sleep, 2003, vol. 26, no. 4, pp. 413–415. https://doi.org/10.1093/sleep/26.4.413

5. Cohrs, S., Sleep disturbances in patients with schizophrenia, CNS Drugs, 2008, vol. 22, no. 11, pp. 939–962. https://doi.org/10.2165/00023210-200822110-00004

6. Dallaspezia, S., Locatelli, C., Lorenzi, C., et al., Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression, J. Affect. Disord., 2016, vol. 192, pp. 64–69. https://doi.org/10.1016/j.jad.2015.11.039

7. Dibner, C., Schibler, U., and Albrecht, U., The mammalian circadian timing system: organization and coordination of central and peripheral clocks, Annu. Rev. Physiol., 2010, vol. 72, pp. 517–549. https://doi.org/10.1146/annurev-physiol-021909-135821

8. Ebisawa, T., Uchiyama, M., Kajimura, N., et al., Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome, EMBO Rep., 2001, vol. 2, no. 4, pp. 342–346. https://doi.org/10.1093/embo-reports/kve070

9. Goel, N., Banks, S., Mignot, E., et al., PER3 polymorphism predicts cumulative sleep homeostatic but not neurobehavioral changes to chronic partial sleep deprivation, PLoS One, 2009, vol. 4, no. 6. e5874. https://doi.org/10.1371/journal.pone.0005874

10. Hida, A., Kitamura, S., Katayose, Y., et al., Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness–eveningness preference and circadian rhythm sleep disorder, Sci. Rep., 2014, vol. 4, p. 6309. https://doi.org/10.1038/srep06309

11. Jones, K.H., Ellis, J., Von Schantz, M., et al., Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities, J. Sleep Res., 2007, vol. 16, no. 1, pp. 12–16. https://doi.org/10.1111/j.1365-2869.2007.00561.x

12. Karthikeyan, R., Marimuthu, G., Chellamuthu Ramasubramanian, G.A., et al., Association of Per3 length polymorphism with bipolar I disorder and schizophrenia, Neuropsychiatric Dis. Treat., 2014, vol. 10, pp. 2325–2330. https://doi.org/10.2147/NDT.S73765

13. Kishi, T., Kitajima, T., Ikeda, M., et al., Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population, Eur. Arch. Psychiatry Clin. Neurosci., 2009, vol. 259, no. 5, pp. 293–297. https://doi.org/10.1007/s00406-009-0869-4

14. Koch, C.E., Leinweber, B., Drengberg, B.C., et al., Interaction between circadian rhythms and stress, Neurobiol. Stress, 2017, vol. 8, no. 6, pp. 57–67. https://doi.org/10.1016/j.ynstr.2016.09.001

15. Lane, J.M., Vlasac, I., Anderson, S.G., et al., Genome-wide association analysis identifies novel loci for chronotype in 100420 individuals from the UK Biobank, Nat. Commun., 2016, vol. 7, p. 10889. https://doi.org/10.1038/ncomms10889

16. Lee, C., Weaver, D.R., and Reppert, S.M., Direct association between mouse

17. PERIOD and CKIε is critical for a functioning circadian clock, Mol. Cell Biol., 2004, vol. 24, no. 2, pp. 584–594. https://doi.org/10.1128/mcb.24.2.584-594.2004

18. Maglione, J.E., Nievergelt, C.M., Parimi, N., et al., Associations of PER3 and RORA circadian gene polymorphisms and depressive symptoms in older adults, Am. J. Geriatr. Psychiatry, 2015, vol. 23, no. 10, pp. 1075–1087. https://doi.org/10.1016/j.jagp.2015.03.002

19. Mansour, H.A., Wood, J., and Logue, T., Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia, Genes Brain Behav., 2006, vol. 5, no. 2, pp. 150–157. https://doi.org/10.1111/j.1601-183X.2005.00147.x

20. Morgan, R. and Cheadle, A., Circadian body temperature in chronic schizophrenia, Br. J. Psychiatry, 1976, vol. 129, no. 4, pp. 350–354. https://doi.org/10.1192/bjp.129.4.350

21. Rao, M.L., Gross, G., Strebel, B., et al., Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia, Biol. Psychiatry, 1994, vol. 35, no. 3, pp. 151–163. https://doi.org/10.1016/0006-3223(94)91147-9

22. Saha, S., Chant, D., Welham, J., et al., A systematic review of the prevalence of schizophrenia, PLoS Med., 2005, vol. 2, no. 5. e141. https://doi.org/10.1371/journal.pmed.0020141

23. Sun, H.Q., Li, S.X., Chen, F.B., et al., Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients, Psychoneuroendocrinology, 2016, vol. 64, pp. 108–116. https://doi.org/10.1016/j.psyneuen.2015.11.013

24. Takahashi, J.S., Transcriptional architecture of the mammalian circadian clock, Nat. Rev. Genet., 2017, vol. 18, no. 3, p. 164. https://doi.org/10.1038/nrg.2016.150

25. Takao, T., Tachikawa, H., Kawanishi, Y., et al., CLOCK gene T3111C polymorphism is associated with Japanese schizophrenics: a preliminary study, Eur. Neuropsychopharmacol., 2006, vol. 17, no. 4, pp. 273–276. https://doi.org/10.1016/j.euroneuro.2006.09.002

26. Viena, T.D., Gobin, C.M., Fins, A.I., et al., A PER3 polymorphism interacts with sleep duration to influence transient mood states in women, J. Circadian Rhythms, 2016, vol. 14, no. 1, p. 3. https://doi.org/10.5334/jcr.135

27. Viola, A.U., Archer, S.N., James, L.M., et al., PER3 polymorphism predicts sleep structure and waking performance, Curr. Biol., 2007, vol. 17, no. 7, pp. 613–618. https://doi.org/10.1016/j.cub.2007.01.073

28. Zhang, J., Liao, G., Liu, C., et al., The association of CLOCK gene T3111C polymorphism and hPER3 gene 54-nucleotide repeat polymorphism with Chinese Han people schizophrenics, Mol. Biol. Rep., 2011, vol. 38, pp. 349–354. https://doi.org/10.1007/s11033-010-0114-2

29. Zhang, L., Hirano, A., Hsu, P.K., et al., A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait, Proc. Natl. Acad. Sci. U. S. A., 2016, vol. 113, no. 11, pp. 1536–1544. https://doi.org/10.1073/pnas.1600039113

30. Zylka, M.J., Shearman, L.P., Weaver, D.R., et al., Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain, Neuron, 1998, vol. 20, no. 6, pp. 1103–1110. https://doi.org/10.1016/S0896-6273(00)80492-4