PDE4B gene polymorphism in Russian patients with panic disorder

Abstract

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.

Keywords

PDE4B gene - rs10454453 - rs502958 - rs1040716 - panic disorder - genetic association

Publication History

Received: 25 June 2019

Accepted: 03 August 2019

Article published online:
31 March 2021

• References

• 1 Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001; 158: 1568-1578
• 2 Jeong Kim E, Kim YK. Panic disorders: The role of genetics and epigenetics. AIMS Genet 2018; 5: 177-190
• 3 O'Donnell JM, Frith S. Behavioral effects of family-selective inhibitors of cyclic nucleotide phosphodiesterases. Pharmacol Biochem Behav 1999; 63: 185-192
• 4 Davis RL, Cherry J, Dauwalder B. et al. The cyclic AMP system and Drosophila learning. Mol Cell Biochem 1995; 149–150: 271-278
• 5 Millar JK, Pickard BS, Mackie S. et al. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 2005; 310: 1187-1191
• 6 Pickard BS, Thomson PA, Christoforou A. et al. The PDE4B gene confers sex-specific protection against schizophrenia. Psychiatr Genet 2007; 17: 129-133
• 7 Fatemi SH, King DP, Reutiman TJ. et al. PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia. Schizophr Res 2008; 101: 36-49
• 8 Numata S, Ueno S, Iga J. et al. Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population. J Psychiatr Res 2008; 43: 7-12
• 9 Kahler AK, Otnaess MK, Wirgenes KV. et al. Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 86-96
• 10 Numata S, Iga J, Nakataki M. et al. 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 2009; 150B: 527-534
• 11 Millar JK, Mackie S, Clapcote SJ. et al. Disrupted in schizophrenia 1 and phosphodiesterase 4B: Towards an understanding of psychiatric illness. J Physiol 2007; 584: 401-405
• 12 Tropea D, Hardingham N, Millar K. et al. Mechanisms underlying the role of DISC1 in synaptic plasticity. J Physiol 2018; 596: 2747-2771
• 13 Cherry JA, Davis RL. Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J Comp Neurol 1999; 407: 287-301
• 14 Charney DS, Deutch A. A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders. Crit Rev Neurobiol 1996; 10: 419-446
• 15 Pandey SC, Zhang H, Roy A. et al. Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest 2005; 115: 2762-2773
• 16 Li YF, Huang Y, Amsdell SL. et al. 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 2009; 34: 2404-2419
• 17 Silvestre JS, Fernandez AG, Palacios JM. Effects of rolipram on the elevated plus-maze test in rats: A preliminary study. J Psychopharmacol 1999; 13: 274-277
• 18 Rutter AR, Poffe A, Cavallini P. et al. 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 2014; 350: 153-163
• 19 Malberg JE, Eisch AJ, Nestler EJ. et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-9110
• 20 Dlaboga D, Hajjhussein H, O'Donnell JM. Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: comparison with rolipram. Brain Res 2006; 1096: 104-112
• 21 Cherry JA, Thompson BE, Pho V. Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse. Biochim Biophys Acta 2001; 1518: 27-35
• 22 Zhang HT, Huang Y, Masood A. et al. Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B). Neuropsychopharmacology 2008; 33: 1611-1623
• 23 Otowa T, Kawamura Y, Sugaya N. et al. Association study of PDE4B with panic disorder in the Japanese population. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 545-549
• 24 Feng Y, Cheng D, Zhang C. et al. Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies. PLoS One 2016; 11: e0147092
• 25 Abramson JH. WINPEPI updated: Computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov 2011; 8: 1
• 26 Favorov AV, Andreewski TV, Sudomoina MA. et al. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans. Genetics 2005; 171: 2113-2121
• 27 Desmet FO, Hamroun D, Lalande M. et al. Human Splicing Finder: An online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009; 37: e67
• 28 Clarke TK, Adams MJ, Davies G. et al. Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N = 112, 117). Mol Psychiatry 2017; 22: 1376-1384
• 29 Meshberg-Cohen S, Svikis D. Panic disorder, trait anxiety, and alcohol use in pregnant and nonpregnant women. Compr Psychiatry 2007; 48: 504-510
• 30 Marquez M, Segui J, Canet J. et al. Alcoholism in 274 patients with panic disorder in Spain, one of the main producers of wine worldwide. J Affect Disord 2003; 75: 237-245
• 31 McNamara D. Panic Attack/Alcohol Use Association Greater in Men. Clinical Psychiatry News 2006; 34: 43
• 32 Bae JS, Park BL, Cheong HS. et al. Association analysis of PDE4B polymorphisms with schizophrenia and smooth pursuit eye movement abnormality in a Korean population. Gen Physiol Biophys 2015; 34: 277-284
• 33 Zhang L, Chen C, He C. et al. Association study of schizophrenia and phosphodiesterase 4B gene polymorphism. Chin J Behav Med Brain Sci 2010; 19: 429-431
• 34 Guan F, Zhang C, Wei S. et al. Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese. Hum Genet 2012; 131: 1047-1056