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Taq1A polymorphism in the dopamine D2 receptor gene predicts brain metabolic response to aripiprazole in healthy male volunteers.

Authors
 Euitae Kim  ;  Jun Soo Kwon  ;  Yong-Wook Shin  ;  Jae Sung Lee  ;  Won Jun Kang  ;  Hang Joon Jo  ;  Jong-Min Lee  ;  Kyung-Sang Yu  ;  Do-Hyung Kang  ;  Joo-Youn Cho  ;  In-Jin Jang  ;  Sang-Goo Shin 
Citation
 PHARMACOGENETICS AND GENOMICS, Vol.18(2) : 91-97, 2008 
Journal Title
PHARMACOGENETICS AND GENOMICS
ISSN
 1744-6872 
Issue Date
2008
MeSH
Adult ; Antipsychotic Agents/pharmacology* ; Aripiprazole ; Base Sequence ; Brain/drug effects* ; Brain/metabolism ; Cross-Over Studies ; DNA Primers ; Humans ; Male ; Piperazines/pharmacology* ; Placebos ; Polymorphism, Genetic* ; Quinolones/pharmacology* ; Receptors, Dopamine D2/genetics* ; Reference Values ; Single-Blind Method ; Taq Polymerase/genetics*
Keywords
antipsychotics ; aripiprazole ; dopamine receptor D2 ; pharmacogenetics ; positron emission tomography ; Taq1A
Abstract
OBJECTIVE: The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene has been reported to be associated with the pharmacodynamics of antipsychotic drugs. We investigated the metabolic response of glucose in the brain to aripiprazole in relation to the DRD2 Taq1A polymorphism.

METHODS: Twenty healthy male volunteers were recruited and were divided into two groups of 10 participants, according to their DRD2 genotypes (A1A1, n=10; A2A2, n=10). The volunteers received single oral doses of aripiprazole (10 mg) and a placebo, following a single-blind, placebo-controlled, randomized, two-way crossover study design. Brain glucose metabolism was assessed using positron emission tomography, scanned with 18F-fluorodeoxyglucose 12 h after the administration of the drug or placebo.

RESULTS: In voxel-based analysis using SPM2, volunteers with the A2A2 genotype showed decreased metabolism in the right middle frontal gyrus, the left middle and inferior frontal gyrus, the right and left inferior temporal gyrus, and the right cingulate gyrus, and increased metabolism in the pons. In contrast, volunteers with the A1A1 genotype exhibited increased metabolism in the right caudate head, and no brain region showed decreased metabolism. In a region-of-interest analysis, significant interactions between drug and genotype were observed in the right medial orbitofrontal gyrus and the left caudate nucleus.

CONCLUSIONS: This suggests that DRD2 Taq1A polymorphism status may be associated with the clinical response to aripiprazole
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01213011-200802000-00002&LSLINK=80&D=ovft
DOI
10.1097/FPC.0b013e3282f3ef8c
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Won Jun(강원준) ORCID logo https://orcid.org/0000-0002-2107-8160
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108361
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