Adenosine A2a Receptor Polymorphisms and Susceptibility to Anxiety Disorders
Iranian Journal of Child Neurology,
Vol. 18 No. 4 (2024),
29 September 2024
,
Page 9-21
https://doi.org/10.22037/ijcn.v18i4.43928
Abstract
Anxiety disorders (ADs) are a group of mental disorders characterized by feelings of tension, fear, and excessive worrying in the face of life experiences. Aberrant signaling of adenosine A2a receptor (ADORA2A) is believed to be involved in the pathogenesis of ADs. Polymorphisms in the ADORA2A gene were shown to be associated with some of the patterns presented by ADs. The results of these studies have been inconsistent, making it hard to draw definitive conclusions. Therefore, this study performed a systematic review to clarify the associations between ADORA2A gene polymorphisms and ADs susceptibility. PubMed/Medline, Web of Science, and Scopus database using appropriate keywords, then screened for separation of suitable studies based on inclusion/exclusion criteria. Collectively, rs5751876 (1976T>C or previously 1083C>T) and rs35060421 (2592C>Tins) polymorphisms of ADORA2A were associated with an increased susceptibility to ADs. Moreover, rs2298383 TT genotype may be the causal regulatory factor, and ADORA2A T/C (rs2298383/rs3761422) haplotypes have significant susceptibility to ADs development. Additional research is needed to further define the role of ADORA2A gene polymorphisms in the pathogenesis of ADs.
- Anxiety disorders, Adenosine, genetic polymorphism, Adenosine A2a receptor
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References
Baxter AJ, Scott KM, Vos T, Whiteford HA. Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychological medicine. 2013;43(5):897-910.
Smoller JW, Gardner‐Schuster E, Covino J, editors. The genetic basis of panic and phobic anxiety disorders. American Journal of Medical Genetics Part C: Seminars in Medical Genetics; 2008: Wiley Online Library.
Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues in clinical neuroscience. 2022.
Meuret AE, Tunnell N, Roque A. Anxiety disorders and medical comorbidity: treatment implications. Anxiety disorders: Rethinking and understanding recent discoveries. 2020:237-61.
Adwas AA, Jbireal J, Azab AE. Anxiety: Insights into signs, symptoms, etiology, pathophysiology, and treatment. East African Scholars Journal of Medical Sciences. 2019;2(10):580-91.
Yamada K, Kobayashi M, Kanda T. Involvement of adenosine A2A receptors in depression and anxiety. International Review of Neurobiology. 2014;119:373-93.
Rosin DL, Hettinger BD, Lee A, Linden J. Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology. 2003;61(11 suppl 6):S12-S8.
Shahrestanaki MK, Arasi FP, Aghaei M. IPP-1 controls Akt/CREB phosphorylation extension in A2a adenosine receptor signaling cascade in MIN6 pancreatic β-cell line. European Journal of Pharmacology. 2019;850:88-96.
Freitag CM, Agelopoulos K, Huy E, Rothermundt M, Krakowitzky P, Meyer J, et al. Adenosine A 2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder. European child & adolescent psychiatry. 2010;19:67-74.
Hohoff C, Mullings EL, Heatherley SV, Freitag CM, Neumann LC, Domschke K, et al. Adenosine A2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality. Journal of psychiatric research. 2010;44(14):930-7.
Hohoff C, Garibotto V, Elmenhorst D, Baffa A, Kroll T, Hoffmann A, et al. Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain. Neuropsychopharmacology. 2014;39(13):2989-99.
Childs E, Hohoff C, Deckert J, Xu K, Badner J, De Wit H. Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 2008;33(12):2791-800.
Rogers PJ, Hohoff C, Heatherley SV, Mullings EL, Maxfield PJ, Evershed RP, et al. Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology. 2010;35(9):1973-83.
Gajewska A, Blumenthal TD, Winter B, Herrmann MJ, Conzelmann A, Mühlberger A, et al. Effects of ADORA2A gene variation and caffeine on prepulse inhibition: a multi-level risk model of anxiety. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;40:115-21.
Domschke K, Gajewska A, Winter B, Herrmann MJ, Warrings B, Mühlberger A, et al. ADORA2A gene variation, caffeine, and emotional processing: a multi-level interaction on startle reflex. Neuropsychopharmacology. 2012;37(3):759-69.
Lam P, Hong C-J, Tsai S-J. Association study of A2a adenosine receptor genetic polymorphism in panic disorder. Neuroscience letters. 2005;378(2):98-101.
Yamada K, Hattori E, Shimizu M, Sugaya A, Shibuya H, Yoshikawa T. Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. Journal of neural transmission. 2001;108:837-48.
Alsene K, Deckert J, Sand P, de Wit H. Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 2003;28(9):1694-702.
Deckert J, Nöthen M, Franke P, Delmo C, Fritze J, Knapp M, et al. Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Molecular psychiatry. 1998;3(1):81-5.
Hamilton SP, Slager SL, De Leon AB, Heiman GA, Klein DF, Hodge SE, et al. Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsychopharmacology. 2004;29(3):558-65.
Hohoff C, Domschke K, Schwarte K, Spellmeyer G, Vögele C, Hetzel G, et al. Sympathetic activity relates to adenosine A 2A receptor gene variation in blood-injury phobia. Journal of neural transmission. 2009;116:659-62.
Hohoff C, Kroll T, Zhao B, Kerkenberg N, Lang I, Schwarte K, et al. ADORA2A variation and adenosine A1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation. Translational Psychiatry. 2020;10(1):406.
Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, de Wit H. Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2005;139(1):42-4.
Erblang M, Drogou C, Gomez-Merino D, Metlaine A, Boland A, Deleuze JF, et al. The impact of genetic variations in ADORA2A in the association between caffeine consumption and sleep. Genes. 2019;10(12):1021.
Geiger MJ, Domschke K, Homola GA, Schulz SM, Nowak J, Akhrif A, et al. ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network. European Neuropsychopharmacology. 2016;26(8):1274-85.
Hohoff C, Marziniak M, Lesch K, Deckert J, Sommer C, Mössner R. An adenosine A2A receptor gene haplotype is associated with migraine with aura. Cephalalgia. 2007;27(2):177-81.
Yu L, Frith MC, Suzuki Y, Peterfreund RA, Gearan T, Sugano S, et al. Characterization of genomic organization of the adenosine A2A receptor gene by molecular and bioinformatics analyses. Brain research. 2004;1000(1-2):156-73.
Fraporti TT, Contini V, Tovo-Rodrigues L, Recamonde-Mendoza M, Rovaris DL, Rohde LA, et al. Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2019;93:214-20.
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