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

Deckert, Jürgen; Nöthen, Markus M.; Franke, Petra; Delmo, Cynthia D.; Fritze, Jürgen; Knapp, Michael; Maier, Wolfgang; Beckmann, H.; Propping, Peter

doi:10.1038/sj.mp.4000345

Cited by 157 publications

(103 citation statements)

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“…Interestingly, the T allele of rs5751876 1976C/T has previously been associated with PD, a condition characterized by attacks of fear and anxiety. Deckert et al (1998) found that PD patients had a higher prevalence of the 1976 T allele compared to controls. Hamilton et al (2004) also report an association between this locus and susceptibility to PD.…”

Section: Discussionmentioning

confidence: 97%

“…Eight SNPs were chosen for genotyping the long form of ADORA2A (25 kb, UCSC Genome Browser, Human Mar.2006 Assembly) based on previous association studies (Alsene et al, 2003;Deckert et al, 1998) and the Hapmap database (rel no. 16, on NCBI B34 assembly, dbSNP b124, http://www.hapmap.org).…”

Section: Genotypingmentioning

confidence: 99%

“…In this study, individuals with the T/T genotype of the ADORA2A SNP rs5751876 (1976C/T) reported greater anxiety after 150 mg caffeine compared to other genotypic groups. The same polymorphism has been linked to panic disorder (PD) (Deckert et al, 1998;Hamilton et al, 2004), suggesting that this variant confers a risk for anxiety states in general. Recently, we have also reported that individuals with the 1976T/T genotype also experience more anxiety after acute doses of the prototypic stimulant drug, D-amphetamine (Hohoff et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Childs

Hohoff

Deckert

et al. 2008

Neuropsychopharmacol

221

170

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Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A 1 and A 2A receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A 2A (ADORA2A) and DRD 2 (DRD2) receptors. Healthy male and female individuals (n ¼ 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3 0 -flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.

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Section: Discussionmentioning

confidence: 97%

Section: Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Childs

Hohoff

Deckert

et al. 2008

Neuropsychopharmacol

221

170

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“…Genotyping assay conditions and primer-probe sequences from all TaqMan and RFLP assays are available on request. ADORA2A SNP rs2298383 and ADORA1 SNP rs10920568, which failed TaqMan assay design, were genotyped by RFLP assays as previously described (Deckert et al, 1998;Freitag et al, 2010). Overall, genotyping resulted in averaged call rates of 100% (range 99.5-100.0), and all genotypes from TaqMan and RFLP analysis were assigned blind regarding group assignment and the measured phenotypic characteristics of the participants.…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

“…Single nucleotide polymorphism selection was based on previous studies (Alsene et al, 2003;Childs et al, 2008;Deckert et al, 1998), and their regulatory potential (UCSC, http://genome.ucsc.edu), linkage disequilibrium (LD) and tagging capabilities (Hapmap, http://www.hapmap.org), and minor allele frequencies. Eight SNPs were selected to cover the 25 kb ADORA2A variant resulting in mRNA X68486 (rs5751862, rs5760405, New3, rs11704959, rs2298383, rs3761422, rs2267076, and rs5751876), and nine SNPs were selected to cover the 76 kb ADORA1 variant resulting in mRNA L22214 (rs9660662, rs1874142, rs10920568, rs12135643, rs3766566, rs3766560, rs3753472, rs16851030, and rs12744240).…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

Rogers

Hohoff

Heatherley

et al. 2010

Neuropsychopharmacol

190

141

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Caffeine, a widely consumed adenosine A 1 and A 2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline.

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An association study of polymorphisms in the alpha-antichymotrypsin gene for Alzheimer disease in Han-Chinese

Meng

et al. 2000

Hum. Mutat.

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Polymerase chain reaction‐denaturing gradient gel electrophoresis (PCR‐DGGE) and DNA sequencing were employed to screen the coding region of the alpha‐antichymotrypsin (AACT) gene in Han‐Chinese population for polymorphism possibly associated with Alzheimer's disease (AD). Consequently, seven polymorphic sites including 25A>G, 39G>A, 370C>T, 662T>G, 892C>T, 923T>C and 1332A>G were detected. Of them, the 25A>G was reported previously and the others are all novel. We subsequently focused on the 25A>G and the 39G>A polymorphism that were of interest to us and conducted an association study of them by another scanning of 246 controls that matched the AD patients. Statistic test showed that both genotype (p=0.0378, Fisher's exact, two tailed) and allele frequency (p=0.0382, Fisher's exact, two tailed) of 39G>A are different between AD patients and the controls. As for 25A>G, lain only the heterozygous genotype A/G associates with AD (p=0.0220, χ2), but not the A allele frequency (p=0.1141, χ2). Hum Mutat 16:275–276, 2000. © 2000 Wiley‐Liss, Inc.

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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

Cited by 157 publications

References 4 publications

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

An association study of polymorphisms in the alpha-antichymotrypsin gene for Alzheimer disease in Han-Chinese

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