title: Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status.
abstract: 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.
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Eisenstein
authors.affiliation: Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, 63130.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bogdan
authors.affiliation: Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Latisha
authors.initials: L
authors.lastname: Love-Gregory
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Nadia S
authors.initials: NS
authors.lastname: Corral-Frías
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Koller
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Neurology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Biochemistry, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Moerlein
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Neurology, Washington University in St. Louis, St. Louis, MO, 63110.|Programs in Physical Therapy and Occupational Therapy, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, 63130.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Barch
authors.affiliation: Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110.|Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, 63130.|Department of Neurology, Washington University in St. Louis, St. Louis, MO, 63110.
authors.forename: Tamara
authors.initials: T
authors.lastname: Hershey
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D017089:Ankyrin Repeat / Q000235:genetics*; D001544:Benperidol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C581293:DRD2 protein, human; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C066786:N-methylbenperidol; D001544:Benperidol
keywords: PET; dopamine; rs1800497