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Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status
Author(s) -
Eisenstein Sarah A.,
Bogdan Ryan,
LoveGregory Latisha,
CorralFrías Nadia S.,
Koller Jonathan M.,
Black Kevin J.,
Moerlein Stephen M.,
Perlmutter Joel S.,
Barch Deanna M.,
Hershey Tamara
Publication year - 2016
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21916
Subject(s) - dopamine receptor d2 , medicine , radioligand , allele , endocrinology , dopamine receptor d3 , genotype , chemistry , receptor , biology , genetics , gene
In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 ( DRD2/ANKK1 ) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are nonselective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, ( N ‐[ 11 C]methyl)benperidol ([ 11 C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in two independent samples. Sample 1 ( n = 39) was composed of obese and nonobese adults; sample 2 ( n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5 to 12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1−), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10–14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1− was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R‐selective [ 11 C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states.