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AIMS Genetics

2019, Volume 6, Issue 3: 55-63. doi: 10.3934/genet.2019.3.55
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Research article

PDE4B gene polymorphism in Russian patients with panic disorder

  • 1.
    Lomonosov Moscow State University, Faculty of Biology, Moscow, Russia
  • 2.
    I.I. Mechnikov Research Institute for Vaccines and Sera, Laboratory of molecular immunology, Moscow, Russia
  • 3.
    University Diagnostic Laboratory LLC, Moscow, Russia
  • 4.
    Centre of Theoretical Problems of Physico-Chemical Pharmacology, Laboratory of Physicochemical and Genetic Problems of Dermatology, Russian Academy of Sciences, Moscow, Russia
  • 5.
    University headache clinic LLC, Moscow, Russia
  • 6.
    The Institute of General Pathology and Pathophysiology, Laboratory of Fundamental and Applied Pain Problems, Moscow, Russia
  • 7.
    Center of Experimental Embryology and Reproductive Biotechnologies, Russian Academy of Sciences, Moscow, Russia
  • Published: 20 August 2019
  • Background: Panic disorder is a complex disease of unclear etiology but with an apparent genetic component. PDE4B gene product is involved in many cell processes owing to its function-regulation of the level of a second messenger cAMP. PDE4B gene polymorphism has been shown to be associated with some mental disorders including panic disorder. Aims: The goal of our study was to evaluate the role of 3 SNPs in the PDE4B gene in the development of panic disorder. Methods: 94 patients diagnosed with panic disorder according to the DSM-IV criteria were enrolled in the study. The population control group included 192 subjects. Genotyping was carried out by real-time PCR with TaqMan probes. Results: The investigated substitutions are not associated with panic disorder in general and in female/male cohorts (p > 0.05). The analysis of complex genotypes demonstrated two protective complex genotypes (rs1040716:A, T + rs10454453:A + rs502958:A and rs1040716:A, T + rs502958:A) associated with panic disorder in general regardless of the patient’s gender (p < 0.05). These genotypes did not correlate with the patient’s sex. Conclusions: We found two complex protective genotypes associated with panic disorder. This can be due to the fact that predisposition to the disease are associated with other genes, while PDE4B gene polymorphism reduces their effect.

    Citation: Alena V Malakhova, Olga I Rudko, Vladimir V Sobolev, Artemii V Tretiakov, Elena A Naumova, Zarema G Kokaeva, Julia E Azimova, Eugene A Klimov. PDE4B gene polymorphism in Russian patients with panic disorder[J]. AIMS Genetics, 2019, 6(3): 55-63. doi: 10.3934/genet.2019.3.55

    Related Papers:

  • Background: Panic disorder is a complex disease of unclear etiology but with an apparent genetic component. PDE4B gene product is involved in many cell processes owing to its function-regulation of the level of a second messenger cAMP. PDE4B gene polymorphism has been shown to be associated with some mental disorders including panic disorder. Aims: The goal of our study was to evaluate the role of 3 SNPs in the PDE4B gene in the development of panic disorder. Methods: 94 patients diagnosed with panic disorder according to the DSM-IV criteria were enrolled in the study. The population control group included 192 subjects. Genotyping was carried out by real-time PCR with TaqMan probes. Results: The investigated substitutions are not associated with panic disorder in general and in female/male cohorts (p > 0.05). The analysis of complex genotypes demonstrated two protective complex genotypes (rs1040716:A, T + rs10454453:A + rs502958:A and rs1040716:A, T + rs502958:A) associated with panic disorder in general regardless of the patient’s gender (p < 0.05). These genotypes did not correlate with the patient’s sex. Conclusions: We found two complex protective genotypes associated with panic disorder. This can be due to the fact that predisposition to the disease are associated with other genes, while PDE4B gene polymorphism reduces their effect.


    加载中

    Abbreviation PD: Panic disorder; PDE: Phosphodiesterases; PDE4B: Phosphodiesterase 4 subtype B;
    Acknowledgments


    We would like to thank all patients for their participation in this study. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

    Conflict of interest


    The authors declare no conflict of interest.

    [1] Hettema JM, Neale MC, Kendler KS (2001) A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158: 1568–1578. doi: 10.1176/appi.ajp.158.10.1568
    [2] Jeong Kim E, Kim YK (2018) Panic disorders: The role of genetics and epigenetics. AIMS Genet 5: 177–190. doi: 10.3934/genet.2018.3.177
    [3] O'Donnell JM, Frith S (1999) Behavioral effects of family-selective inhibitors of cyclic nucleotide phosphodiesterases. Pharmacol Biochem Behav 63: 185–192. doi: 10.1016/S0091-3057(98)00267-6
    [4] Davis RL, Cherry J, Dauwalder B, et al. (1995) The cyclic AMP system and Drosophila learning. Mol Cell Biochem 149–150: 271–278.
    [5] Millar JK, Pickard BS, Mackie S, et al. (2005) DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310: 1187–1191. doi: 10.1126/science.1112915
    [6] Pickard BS, Thomson PA, Christoforou A, et al. (2007) The PDE4B gene confers sex-specific protection against schizophrenia. Psychiatr Genet 17: 129–133. doi: 10.1097/YPG.0b013e328014492b
    [7] Fatemi SH, King DP, Reutiman TJ, et al. (2008) PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia. Schizophr Res 101: 36–49. doi: 10.1016/j.schres.2008.01.029
    [8] Numata S, Ueno S, Iga J, et al. (2008) Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population. J Psychiatr Res 43: 7–12. doi: 10.1016/j.jpsychires.2008.01.013
    [9] Kahler AK, Otnaess MK, Wirgenes KV, et al. (2010) Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples. Am J Med Genet B Neuropsychiatr Genet 153B: 86–96.
    [10] Numata S, Iga J, Nakataki M, et al. (2009) Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population. Am J Med Genet B Neuropsychiatr Genet 150B: 527–534. doi: 10.1002/ajmg.b.30852
    [11] Millar JK, Mackie S, Clapcote SJ, et al. (2007) Disrupted in schizophrenia 1 and phosphodiesterase 4B: Towards an understanding of psychiatric illness. J Physiol 584: 401–405. doi: 10.1113/jphysiol.2007.140210
    [12] Tropea D, Hardingham N, Millar K, et al. (2018) Mechanisms underlying the role of DISC1 in synaptic plasticity. J Physiol 596: 2747–2771. doi: 10.1113/JP274330
    [13] Cherry JA, Davis RL (1999) Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J Comp Neurol 407: 287–301. doi: 10.1002/(SICI)1096-9861(19990503)407:2<287::AID-CNE9>3.0.CO;2-R
    [14] Charney DS, Deutch A (1996) A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders. Crit Rev Neurobiol 10: 419–446. doi: 10.1615/CritRevNeurobiol.v10.i3-4.70
    [15] Pandey SC, Zhang H, Roy A, et al. (2005) Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest 115: 2762–2773. doi: 10.1172/JCI24381
    [16] Li YF, Huang Y, Amsdell SL, et al. (2009) Antidepressant- and anxiolytic-like effects of the phosphodiesterase-4 inhibitor rolipram on behavior depend on cyclic AMP response element binding protein-mediated neurogenesis in the hippocampus. Neuropsychopharmacology 34: 2404–2419. doi: 10.1038/npp.2009.66
    [17] Silvestre JS, Fernandez AG, Palacios JM (1999) Effects of rolipram on the elevated plus-maze test in rats: A preliminary study. J Psychopharmacol 13: 274–277. doi: 10.1177/026988119901300309
    [18] Rutter AR, Poffe A, Cavallini P, et al. (2014) GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical species. J Pharmacol Exp Ther 350: 153–163. doi: 10.1124/jpet.114.214155
    [19] Malberg JE, Eisch AJ, Nestler EJ, et al. (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20: 9104–9110. doi: 10.1523/JNEUROSCI.20-24-09104.2000
    [20] Dlaboga D, Hajjhussein H, O'Donnell JM (2006) Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: comparison with rolipram. Brain Res 1096: 104–112. doi: 10.1016/j.brainres.2006.04.032
    [21] Cherry JA, Thompson BE, Pho V (2001) Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse. Biochim Biophys Acta 1518: 27–35. doi: 10.1016/S0167-4781(01)00164-6
    [22] Zhang HT, Huang Y, Masood A, et al. (2008) Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B). Neuropsychopharmacology 33: 1611–1623. doi: 10.1038/sj.npp.1301537
    [23] Otowa T, Kawamura Y, Sugaya N, et al. (2011) Association study of PDE4B with panic disorder in the Japanese population. Prog Neuropsychopharmacol Biol Psychiatry 35: 545–549. doi: 10.1016/j.pnpbp.2010.12.013
    [24] Feng Y, Cheng D, Zhang C, et al. (2016) Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies. PLoS One 11: e0147092. doi: 10.1371/journal.pone.0147092
    [25] Abramson JH (2011) WINPEPI updated: Computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov 8: 1. doi: 10.1186/1742-5573-8-1
    [26] Favorov AV, Andreewski TV, Sudomoina MA, et al. (2005) A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans. Genetics 171: 2113–2121. doi: 10.1534/genetics.105.048090
    [27] Desmet FO, Hamroun D, Lalande M, et al. (2009) Human Splicing Finder: An online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37: e67. doi: 10.1093/nar/gkp215
    [28] Clarke TK, Adams MJ, Davies G, et al. (2017) Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N = 112, 117). Mol Psychiatry 22: 1376–1384. doi: 10.1038/mp.2017.153
    [29] Meshberg-Cohen S, Svikis D (2007) Panic disorder, trait anxiety, and alcohol use in pregnant and nonpregnant women. Compr Psychiatry 48: 504–510. doi: 10.1016/j.comppsych.2007.06.004
    [30] Marquez M, Segui J, Canet J, et al. (2003) Alcoholism in 274 patients with panic disorder in Spain, one of the main producers of wine worldwide. J Affect Disord 75: 237–245. doi: 10.1016/S0165-0327(02)00054-X
    [31] McNamara D (2006) Panic Attack/Alcohol Use Association Greater in Men. Clinical Psychiatry News 34: 43.
    [32] Bae JS, Park BL, Cheong HS, et al. (2015) Association analysis of PDE4B polymorphisms with schizophrenia and smooth pursuit eye movement abnormality in a Korean population. Gen Physiol Biophys 34: 277–284. doi: 10.4149/gpb_2015004
    [33] Zhang L, Chen C, He C, et al. (2010) Association study of schizophrenia and phosphodiesterase 4B gene polymorphism. Chin J Behav Med Brain Sci 19: 429–431.
    [34] Guan F, Zhang C, Wei S, et al. (2012) Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese. Hum Genet 131: 1047–1056. doi: 10.1007/s00439-011-1120-8
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  • © 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
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