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DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.

ABSTRACT: The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D(2/3) receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D(2/3) receptor binding in depressed patients as well as the SNP's effect on D(2/3) binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [(11)C]raclopride, once without receiving monetary rewards (baseline) and once while winning money. In Con, the A1 allele was associated with reduced baseline binding potential (BP(ND)) in the middle caudate and ventral striatum. However, in MDD patients the A1 allele was associated with increased baseline BP(ND) in these regions. There were no significant associations between rs1800497 and change in BP(ND) during reward-associated dopamine release. Conceivably, the A1 allele predisposes to depression and addiction via its effect on the post-synaptic D(2) receptor.

SUBMITTER: Savitz J

PROVIDER: S-EPMC3758772 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.

Savitz Jonathan J Hodgkinson Colin A CA Martin-Soelch Chantal C Shen Pei-Hong PH Szczepanik Joanna J Nugent Allison C AC Herscovitch Peter P Grace Anthony A AA Goldman David D Drevets Wayne C WC

The international journal of neuropsychopharmacology 20130520 9

The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D(2/3) receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D(2/3) receptor binding in depressed patients as well as the SNP's effect on D(2/3) binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [(11)C]raclopride, once with ...[more]

PMID: 23683269

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Project description:BackgroundPrevious studies suggested that single-nucleotide polymorphisms in dopamine receptor D2 (DRD2) are the susceptibility loci for migraine. This study was aimed at evaluating the contribution of DRD2 rs1800497 and its expression to migraine risk in Han Chinese subjects.MethodsIn total, 250 patients with migraine and 250 age- and sex-matched control subjects were included in this study. TaqMan allelic discrimination assay was used for DRD2 rs1800497 genotyping. Plasma DRD2 concentration was determined using enzyme-linked immunosorbent assay.ResultsSignificant associations were observed for the rs1800497 genotype (c2=6.37, p=0.041) and allele (c2=4.69, p=0.03; odds ratio [OR]=1.33, 95% CI=1.03-1.72, power=58%) frequencies between the migraine and control groups. Sex analysis indicated a positive association for rs1800497 between female patients with migraine and control individuals (genotype: c2=7.84, p=0.019; allele: c2=6.60, p=0.010; OR=1.61, 95% CI=1.12-2.30, power=73.4%). Furthermore, a significant association was observed only in female patients with migraine without aura (MO) (genotype: c2=6.88, p=0.032; allele: c2=5.65, p=0.017; OR=1.59, 95% CI=1.08-2.36, power=65.1%). The mean plasma DRD2 levels in the control group (mean±SD: 24.20±2.78) were significantly lower than those in the migraine with aura (MA) (30.86±3.69, p<0.0001) and MO groups (31.88±4.99, p<0.0001). Additionally, there was a sex-based difference in DRD2 expression in the MA (male vs female: 29.46±3.59 vs 32.27±3.27, p<0.01) and MO groups (male vs female: 29.18±3.50 vs 34.58±4.84, p<0.0001). Moreover, plasma DRD2 levels in patients were significantly different among the three genotypes (CC vs CT vs TT: 24.76±3.76 vs 30.93±3.85 vs 37.06±3.95, p<0.0001). Similar results were observed both in the MA (CC vs CT vs TT: 25.09±3.84 vs 28.57±2.84 vs 33.37±1.58, p<0.0001) and MO groups (CC vs CT vs TT: 24.65±3.79 vs 31.65±3.86 vs 38.29±3.74, p<0.0001).ConclusionOur case-control study suggested that the DRD2 polymorphism rs1800497 was significantly associated with the risk of migraine in Han Chinese females. Additionally, the plasma DRD2 level was high in patients with migraine. Females with migraine had considerably higher DRD2 levels than males with migraine. DRD2 expression may be regulated by DRD2 rs1800497 genotype in patients with migraine.

Dataset Information

DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.

Publications

DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.

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