Adenosine receptors are G-protein-coupled receptors involved in a wide range of physiological and pathological phenomena in most mammalian systems. All four receptors are widely expressed in the central nervous system, where they modulate neurotransmitter release and neuronal plasticity. A large number of gene association studies have shown that common genetic variants of the adenosine receptors (encoded by the ADORA1, ADORA2A, ADORA2B, and ADORA3 genes) have a neuroprotective or neurodegenerative role in neurologic/psychiatric diseases. New genetic studies of rare variants and few novel associations with depression or epilepsy subtypes have recently been reported. In this study, we review the literature on the genetics of adenosine receptors in neurologic and/or psychiatric diseases in humans, and discuss perspectives for further genetic research. We also provide an update on the genetic structures of the four human adenosine receptor genes and their regulation—a topic that has not been extensively addressed. Our review emphasizes the importance of (i) better characterizing the genetics of adenosine receptor genes and (ii) understanding how these genes are regulated.
Get full access to this article
View all access options for this article.
References
1.
FredholmBB, ChenJ-F, CunhaRA, et al. Adenosine and brain function. Int Rev Neurobiol. 2005; 63:191–270.
2.
BurnstockG, FredholmBB, VerkhratskyA. Adenosine and ATP receptors in the brain. Curr Top Med Chem. 2011; 11:973–1011.
3.
CunhaRA. How does adenosine control neuronal dysfunction and neurodegeneration?. J Neurochem. 2016; 139:1019–1055.
4.
CiruelaF. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci. 2006; 26:2080–2087.
5.
GinesS, HillionJ, TorvinenM, et al. Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci U S A. 2000; 97:8606–8611.
6.
HillionJ, CanalsM, TorvinenM, et al. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem. 2002; 277:18091–18097.
7.
CunhaRA. Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade. Purinergic Signal. 2005; 1:111–134.
8.
GomesCV, KasterMP, ToméAR, et al. Adenosine receptors and brain diseases: Neuroprotection and neurodegeneration. Biochim Biophys Acta. 2011; 1808:1380–1399.
9.
VecchioEA, WhitePJ, MayLT. The adenosine A2B G protein-coupled receptor: Recent advances and therapeutic implications. Pharmacol Ther. 2019; 198:20–33.
10.
BoreaPA, VaraniK, VincenziF, et al. The A3 adenosine receptor: History and perspectives. Pharmacol Rev. 2014; 67:74–102.
11.
LiuJ, CiarochiJ, CalhounVD, et al. Genetics modulate gray matter variation beyond disease burden in prodromal Huntington's disease. Front Neurol. 2018; 9:190.
12.
CampbellNG, ZhuC-B, LindlerKM, et al. Rare coding variants of the adenosine A3 receptor are increased in autism: On the trail of the serotonin transporter regulome. Mol Autism. 2013; 4:28.
13.
ClarkSL, McClayJL, AdkinsDE, et al. Deep sequencing of 71 candidate genes to characterize variation associated with alcohol dependence. Alcohol Clin Exp Res. 2017; 41:711–718.
14.
ShinoharaM, SaitohM, NishizawaD, et al. ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus. Neurology. 2013; 80:1571–1576.
15.
OliveiraS, ArdaisAP, BastosCR, et al. Impact of genetic variations in ADORA2A gene on depression and symptoms: A cross-sectional population-based study. Purinergic Signal. 2019; 15:37–44.
16.
FredholmBB, ArslanG, HalldnerL, et al. Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol. 2000; 362:364–374.
FerréS, Díaz-RíosM, SalamoneJD, et al. New developments on the adenosine mechanisms of the central effects of caffeine and their implications for neuropsychiatric disorders. J Caffeine Adenosine Res. 2018; 8:121–130.
19.
ChenJ-F. Adenosine receptor control of cognition in normal and disease. Int Rev Neurobiol. 2014; 119:257–307.
20.
Townsend-NicholsonA, ShineJ. Molecular cloning and characterisation of a human brain A1 adenosine receptor cDNA. Brain Res Mol Brain Res. 1992; 16:365–370.
21.
LibertF, Van SandeJ, LefortA, et al. Cloning and functional characterization of a human Al adenosine receptor. Biochem Biophys Res Commun. 1992; 187:919–926.
22.
Townsend-NicholsonA, BakerE, SchofieldPR, et al. Localization of the adenosine A1 receptor subtype gene (ADORA1) to chromosome 1q32.1. Genomics. 1995; 26:423–425.
23.
RenH, StilesGL. Characterization of the human A1 adenosine receptor gene. Evidence for alternative splicing. J Biol Chem. 1994; 269:3104–3110.
24.
RenH, StilesGL. Posttranscriptional mRNA processing as a mechanism for regulation of human A1 adenosine receptor expression. Proc Natl Acad Sci U S A. 1994; 91:4864–4866.
25.
CarithersLJ, ArdlieK, BarcusM, et al. A novel approach to high-quality postmortem tissue procurement: The GTEx project. Biopreserv Biobank. 2015; 13:311–319.
26.
HarrowJ, FrankishA, GonzalezJM, et al. GENCODE: The reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22:1760–1774.
27.
RenH, StilesGL. Separate promoters in the human A1 adenosine receptor gene direct the synthesis of distinct messenger RNAs that regulate receptor abundance. Mol Pharmacol. 1995; 48:975–980.
RenH, StilesGL. Dexamethasone stimulates human A1 adenosine receptor (A1 AR) gene expression through multiple regulatory sites in promoter B. Mol Pharmacol. 1999; 55:309–316.
30.
RenH, StilesGL. A single-stranded DNA binding site in the human A1 adenosine receptor gene promoter. Mol Pharmacol. 1998; 53:43–51.
31.
LeeC, LaiH-L, LeeY-C, et al. The A2A adenosine receptor is a dual coding gene: A novel mechanism of gene usage and signal transduction. J Biol Chem. 2014; 289:1257–1270.
GotohL, MitsuyasuH, KobayashiY, et al. Association analysis of adenosine A1 receptor gene (ADORA1) polymorphisms with schizophrenia in a Japanese population: Psychiatr Genet. 2009; 19:328–335.
34.
JanikP, BerdyńskiM, SafranowK, et al. Association of ADORA1 rs2228079 and ADORA2A rs5751876 polymorphisms with Gilles de la Tourette Syndrome in the Polish population. PLoS One. 2015; 10:e0136754.
35.
DeckertJ, NöthenMM, AlbusM, et al. Adenosine A1 receptor and bipolar affective disorder: Systematic screening of the gene and association studies. Am J Med Genet. 1998; 81:18–23.
36.
KobayashiH, UjikeH, IwataN, et al. Association analysis of the adenosine A1 receptor gene polymorphisms in patients with methamphetamine dependence/psychosis. Curr Neuropharmacol. 2011; 9:137–142.
37.
RogersPJ, HohoffC, HeatherleySV, et al. Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology. 2010; 35:1973–1983.
38.
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511:421–427.
39.
GoesFS, McGrathJ, AvramopoulosD, et al. Genome-wide association study of schizophrenia in Ashkenazi Jews. Am J Med Genet B Neuropsychiatr Genet. 2015; 168:649–659.
40.
YuD, SulJH, TsetsosF, et al. Interrogating the genetic determinants of Tourette's syndrome and other Tic disorders through genome-wide association studies. Am J Psychiatry. 2019; 176:217–227.
41.
TreutleinJ, FrankJ, StreitF, et al. Genetic contribution to alcohol dependence: Investigation of a heterogeneous German sample of individuals with alcohol dependence, chronic alcoholic pancreatitis, and alcohol-related cirrhosis. Genes. 2017; 8:183.
42.
JaberiE, RohaniM, ShahidiGA, et al. Mutation in ADORA1 identified as likely cause of early-onset parkinsonism and cognitive dysfunction: ADORA1 mutation associated with parkinsonism. Mov Disord. 2016; 31:1004–1011.
43.
SatakeW, NakabayashiY, MizutaI, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet. 2009; 41:1303–1307.
44.
Simón-SánchezJ, SchulteC, BrasJM, et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet. 2009; 41:1308–1312.
45.
BlauwendraatC, NallsMA, FederoffM, et al. ADORA1 mutations are not a common cause of Parkinson's disease and dementia with Lewy bodies: Mutational analysis in ADORA1. Mov Disord. 2017; 32:298–299.
46.
KhodadadiH, AzconaLJ, AghamollaiiV, et al. PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism: PTRHD1 mutation in ID and parkinsonism. Mov Disord. 2017; 32:287–291.
47.
ElahiE. PTRHD1 and possibly ADORA1 mutations contribute to Parkinsonism with intellectual disability. Mov Disord. 2018; 33:174.
48.
WagnerAK, MillerMA, ScanlonJ, et al. Adenosine A1 receptor gene variants associated with post-traumatic seizures after severe TBI. Epilepsy Res. 2010; 90:259–272.
49.
FurlongTJ, PierceKD, SelbieLA, et al. Molecular characterization of a human brain adenosine A2 receptor. Brain Res Mol Brain Res. 1992; 15:62–66.
50.
MacCollinM, PeterfreundR, MacDonaldM, et al. Mapping of a human A2a adenosine receptor (ADORA2) to chromosome 22. Genomics. 1994; 20:332–333.
51.
LeF, Townsend-NicholsonA, BakerE, et al. Characterization and chromosomal localization of the human A2a adenosine receptor gene: ADORA2A. Biochem Biophys Res Commun. 1996; 223:461–467.
52.
PeterfreundRA, MacCollinM, GusellaJ, et al. Characterization and expression of the human A2a adenosine receptor gene. J Neurochem. 2002; 66:362–368.
53.
FredholmBB, ChernY, FrancoR, et al. Aspects of the general biology of adenosine A2A signaling. Prog Neurobiol. 2007; 83:263–276.
54.
YuL, FrithMC, SuzukiY, et al. Characterization of genomic organization of the adenosine A2A receptor gene by molecular and bioinformatics analyses. Brain Res. 2004; 1000:156–173.
55.
KrethS, LedderoseC, KaufmannI, et al. Differential expression of 5′-UTR splice variants of the adenosine A2A receptor gene in human granulocytes: Identification, characterization, and functional impact on activation. FASEB J. 2008; 22:3276–3286.
56.
ChuY-Y, TuK-H, LeeYC, et al. Characterization of the rat A2a adenosine receptor gene. DNA Cell Biol. 1996; 15:329–337.
57.
LeeYC, LaiHL, SunCN, et al. Identification of nuclear factor 1 (NF1) as a transcriptional modulator of rat A(2A) adenosine receptor. Brain Res Mol Brain Res. 2003; 111:61–73.
58.
ChiangM-C, LeeY-C, HuangC-L, et al. cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J Biol Chem. 2005; 280:14331–14340.
59.
BrownST, ReyesEP, NurseCA. Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2α: Role in modulating secretion. Biochem Biophys Res Commun. 2011; 412:466–472.
60.
MorelloS, ItoK, YamamuraS, et al. IL-1β and TNF-α regulation of the adenosine receptor (A2A) expression: Differential requirement for NF-κB binding to the proximal promoter. J Immunol. 2006; 177:7173–7183.
61.
AhmadA, AhmadS, GloverL, et al. Adenosine A2A receptor is a unique angiogenic target of HIF-2 in pulmonary endothelial cells. Proc Natl Acad Sci U S A. 2009; 106:10684–10689.
62.
ErnstJ, KellisM. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol. 2010; 28:817–825.
63.
The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489:57–74.
64.
BuiraSP, AlbasanzJL, DentesanoG, et al. DNA methylation regulates adenosine A2A receptor cell surface expression levels. J Neurochem. 2010; 112:1273–1285.
65.
BuiraSP, DentesanoG, AlbasanzJL, et al. DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain: ZBP-89 and Yin Yang-1 control ADORA2A expression. J Neurochem. 2010; 115:283–295.
66.
Villar-MenéndezI, NuñezF, Díaz-SánchezS, et al. Striatal adenosine A2A receptor expression is controlled by S-adenosyl-L-methionine-mediated methylation. Purinergic Signal. 2014; 10:523–528.
67.
Villar-MenéndezI, BlanchM, TyebjiS, et al. Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington's disease. Neuromol Med. 2013; 15:295–309.
68.
Villar-MenéndezI, Díaz-SánchezS, BlanchM, et al. Reduced striatal adenosine A2A receptor levels define a molecular subgroup in schizophrenia. J Psychiatr Res. 2014; 51:49–59.
69.
HinnebuschAG, IvanovIP, SonenbergN. Translational control by 5’-untranslated regions of eukaryotic mRNAs. Science. 2016; 352:1413–1416.
70.
LeeYC, ChangCW, SuCW. The 5’ untranslated regions of the rat A2A adenosine receptor gene function as negative translational regulators. J Neurochem. 2002; 73:1790–1798.
71.
DjebaliS, LagardeJ, KapranovP, et al. Sympathetic activity relates to adenosine A2A receptor gene variation in blood-injury phobia. J Neural Transm. 2012; 7:e28213.
72.
GuennewigB, CooperAA. The central role of noncoding RNA in the brain. Int Rev Neurobiol. 2014; 116:153–194.
73.
BriggsJA, WolvetangEJ, MattickJS, et al. Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron. 2015; 88:861–877.
74.
SaltaE, De StrooperB. Noncoding RNAs in neurodegeneration. Nat Rev Neurosci. 2017; 18:627–640.
75.
DeckertJ, NöthenMM, FrankeP, 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. Mol Psychiatry. 1998; 3:81–85.
76.
HamiltonSP, SlagerSL, de LeonAB, et al. Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsychopharmacology. 2004; 29:558–565.
77.
HohoffC, DomschkeK, SchwarteK, et al. Sympathetic activity relates to adenosine A2A receptor gene variation in blood-injury phobia. J Neural Transm. 2009; 116:659–662.
78.
HohoffC, MullingsEL, HeatherleySV, et al. Adenosine A2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality. J Psychiatr Res. 2010; 44:930–937.
79.
GugliandoloA, GangemiC, CaccamoD, et al. The RS685012 polymorphism of ACCN2, the human ortholog of murine acid-sensing ion channel (ASIC1) gene, is highly represented in patients with panic disorder. Neuromol Med. 2016; 18:91–98.
80.
AlseneK, DeckertJ, SandP, et al. Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 2003; 28:1694–1702.
81.
ChildsE, HohoffC, DeckertJ, et al. Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 2008; 33:2791–2800.
82.
HohoffC, McDonaldJM, BauneBT, et al. Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A2A receptor gene variants. Am J Med Genet B Neuropsychiatr Genet. 2005; 139B:42–44.
83.
DomschkeK, GajewskaA, WinterB, et al. ADORA2A gene variation, caffeine, and emotional processing: A multi-level interaction on startle reflex. Neuropsychopharmacology. 2012; 37:759–769.
84.
GajewskaA, BlumenthalTD, WinterB, et al. Effects of ADORA2A gene variation and caffeine on prepulse inhibition: A multi-level risk model of anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 40:115–121.
85.
RendaG, CommitteriG, ZimarinoM, et al. Genetic determinants of cognitive responses to caffeine drinking identified from a double-blind, randomized, controlled trial. Eur Neuropsychopharmacol. 2015; 25:798–807.
86.
LedentC, VaugeoisJ-M, SchiffmannSN, et al. Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature. 1997; 388:674–678.
87.
LamP, HongC-J, TsaiS-J. Association study of A2a adenosine receptor genetic polymorphism in panic disorder. Neurosci Lett. 2005; 378:98–101.
88.
YamadaK, HattoriE, ShimizuM, et al. Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. J Neural Transm. 2001; 108:837–848.
89.
SubaranRL, TalatiA, HamiltonSP, et al. A survey of putative anxiety-associated genes in panic disorder patients with and without bladder symptoms: Psychiatr Genet. 2012; 22:271–278.
90.
MoleroY, GumpertC, SerlachiusE, et al. A study of the possible association between adenosine A2A receptor gene polymorphisms and attention-deficit hyperactivity disorder traits: Adenosine A2A receptor gene and ADHD traits. Genes Brain Behav. 2013; 12:305–310.
91.
FraportiTT, ContiniV, Tovo-RodriguesL, et al. Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 93:214–220.
92.
FreitagCM, AgelopoulosK, HuyE, et al. Adenosine A2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder. Eur Child Adolesc Psychiatry. 2010; 19:67–74.
93.
JagannathanK, CalhounVD, GelernterJ, et al. Genetic associations of brain structural networks in schizophrenia: A preliminary study. Biol Psychiatry. 2010; 68:657–666.
94.
DeckertJ, NöthenMM, RietschelM, et al. Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia. J Neural Transm. 1996; 103:1447–1455.
95.
HongC-J, LiuH-C, LiuT-Y, et al. Association studies of the adenosine A2a receptor (1976T > C) genetic polymorphism in Parkinson's disease and schizophrenia. J Neural Transm. 2005; 112:1503–1510.
96.
LuuS-U, LiaoH-M, HungT-W, et al. Mutation analysis of adenosine A2a receptor gene and interaction study with dopamine D2 receptor gene in schizophrenia: Psychiatr Genet. 2008; 18:43.
97.
TsaiS-J, HongC-J, HouS-J, et al. Association study of adenosine A2a receptor (1976C>T) genetic polymorphism and mood disorders and age of onset. Psychiatr Genet. 2006; 16:185.
98.
HohoffC, MarziniakM, LeschK-P, et al. An adenosine A2A receptor gene haplotype is associated with migraine with aura. Cephalalgia. 2007; 27:177–181.
99.
DhaenensC-M, BurnoufS, SimoninC, et al. A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease. Neurobiol Dis. 2009; 35:474–476.
100.
Taherzadeh-FardE, SaftC, WieczorekS, et al. Age at onset in Huntington's disease: Replication study on the associations of ADORA2A, HAP1 and OGG1. Neurogenetics. 2010; 11:435–439.
101.
VitalM, BidegainE, RaggioV, et al. Molecular characterization of genes modifying the age at onset in Huntington's disease in Uruguayan patients. Int J Neurosci. 2016; 126:510–513.
102.
SimoninC, DuruC, SalleronJ, et al. Association between caffeine intake and age at onset in Huntington's disease. Neurobiol Dis. 2013; 58:179–182.
103.
BlumD, ChernY, DomeniciMR, et al. The role of adenosine tone and adenosine receptors in Huntington's disease. J Caffeine Adenosine Res. 2018; 8:43–58.
104.
Horgusluoglu-MolochE, NhoK, RisacherSL, et al. Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2017; 60:92–103.
105.
BesteC, StockA-K, NessV, et al. Differential effects of ADORA2A gene variations in pre-attentive visual sensory memory subprocesses. Eur Neuropsychopharmacol. 2012; 22:555–561.
106.
GeigerMJ, DomschkeK, HomolaGA, et al. ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network. Eur Neuropsychopharmacol. 2016; 26:1274–1285.
107.
RuppTL, WesenstenNJ, NewmanR, et al. PER3 and ADORA2A polymorphisms impact neurobehavioral performance during sleep restriction. J Sleep Res. 2013; 22:160–165.
108.
RéteyJV, AdamM, KhatamiR, et al. A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther. 2007; 81:692–698.
109.
BodenmannS, HohoffC, FreitagC, et al. Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation: ADORA2A haplotypes, vigilance and CNS stimulants. Br J Pharmacol. 2012; 165:1904–1913.
110.
ByrneEM, JohnsonJ, McRaeAF, et al. A genome-wide association study of caffeine-related sleep disturbance: Confirmation of a role for a common variant in the adenosine receptor. Sleep. 2012; 35:967–975.
111.
NunesRA, MazzottiDR, HirotsuC, et al. The association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypes. Sleep Med. 2017; 30:210–215.
112.
PierceKD, FurlongTJ, SelbieLA, et al. Molecular cloning and expression of an adenosine A2b receptor from human brain. Biochem Biophys Res Commun. 1992; 187:86–93.
113.
Townsend-NicholsonA, BakerE, SutherlandGR, et al. Localization of the adenosine A2b receptor subtype gene (ADORA2B) to chromosome 17p11.2-p12 by FISH and PCR screening of somatic cell hybrids. Genomics. 1995; 25:605–607.
114.
JacobsonMA, JohnsonRG, LuneauCJ, et al. Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene. Genomics. 1995; 27:374–376.
115.
KongT, WestermanKA, FaigleM, et al. HIF-dependent induction of adenosine A2B receptor in hypoxia. FASEB J. 2006; 20:2242–2250.
116.
EckleT, KewleyEM, BrodskyKS, et al. Identification of hypoxia-inducible factor HIF-1A as transcriptional regulator of the A2B adenosine receptor during acute lung injury. J Immunol. 2014; 192:1249–1256.
117.
YangM, MaC, LiuS, et al. HIF-dependent induction of adenosine receptor A2b skews human dendritic cells to a Th2-stimulating phenotype under hypoxia. Immunol Cell Biol. 2010; 88:165–171.
118.
St. Hilaire C, Yang D, Schreiber BM, et al. B-Myb regulates the A2B adenosine receptor in vascular smooth muscle cells. J Cell Biochem. 2008; 103:1962–1974.
119.
SalvatoreCA, JacobsonMA, TaylorHE, et al. Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci U S A. 1993; 90:10365–10369.
120.
SajjadiFG, FiresteinGS. cDNA cloning and sequence analysis of the human A3 adenosine receptor. Biochim Biophys Acta BBA. 1993; 1179:105–107.
121.
WilkieTM, ChenY, GilbertDJ, et al. Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors. Genomics. 1993; 18:175–184.
122.
MonittoCL, LevittRC, DiSilvestreD, et al. Localization of the A3 adenosine receptor gene (ADORA3) to human chromosome 1p. Genomics. 1995; 26:637–638.
123.
MurrisonE, GoodsonSJ, HarrisCA, et al. The human A3 adenosine receptor gene. Biochem Soc Trans. 1995; 23:270S–270S.
124.
IyerSV, RanjanA, EliasHK, et al. Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression. Nat Commun, 2016; 7:13561.
125.
MurrisonEM, GoodsonSJ, EdbrookeMR, et al. Cloning and characterisation of the human adenosine A3 receptor gene. FEBS Lett. 1996; 384:243–246.
126.
AtkinsonMR, Townsend-NicholsonA, NichollJK, et al. Cloning, characterisation and chromosomal assignment of the human adenosine A3 receptor (ADORA3) gene. Neurosci Res. 1997; 29:73–79.
127.
KimS-H, NamE-J, KimY-K, et al. Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria: ADORA3 gene polymorphism in aspirin-induced urticaria. Br J Dermatol. 2010; 163:977–985.
128.
GoniJR. Triplex-forming oligonucleotide target sequences in the human genome. Nucleic Acids Res. 2004; 32:354–360.
129.
HohoffC, GaribottoV, ElmenhorstD, et al. Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain. Neuropsychopharmacology. 2014; 39:2989–2999.
130.
Borroto-EscuelaDO, HinzS, NavarroG, et al. Understanding the role of adenosine A2AR heteroreceptor complexes in neurodegeneration and neuroinflammation. Front Neurosci, 2018; 12:43.
131.
OtowaT, HekK, LeeM, et al. Meta-analysis of genome-wide association studies of anxiety disorders. Mol Psychiatry. 2016; 21:1391–1399.
132.
WeiCJ, AugustoE, GomesCA, et al. Regulation of fear responses by striatal and extrastriatal adenosine A2A receptors in forebrain. Biol Psychiatry. 2014; 75:855–863.
133.
BodmerW, BonillaC. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. 2008; 40:695–701.
134.
WangL, ShenX, WuY, et al. Coffee and caffeine consumption and depression: A meta-analysis of observational studies. Aust N Z J Psychiatry. 2016; 50:228–242.
135.
GassN, OllilaHM, UtgeS, et al. Contribution of adenosine related genes to the risk of depression with disturbed sleep. J Affect Disord. 2010; 126:134–139.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
