D2 dopamine receptor gene (DRD2) Taql A polymorphism:... : Pharmacogenetics and Genomics (original) (raw)
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D2 dopamine receptor gene (DRD2) Taql A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele
Thompson, J; Thomas, N1; Singleton, A.1; Piggot, M1; Lloyd, S1; Perry, E K1; Morris, C M1; Perry, R H2; Ferrier, I N3; Court, J A1
1MRC Neurochemical Pathology Unit
2Department of Neuropathology, Newcastle General Hospital, westgate Road, Newcastle upon Tyne NE4 6BE,UK
3Department of Psychiatry. Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP. UK
Abstract
The relationship between a dopamine D2 receptor genetic polymorphism at the TaqA A locus and the level of D2 receptor binding was investigated in normal, middle aged to elderly subjects with no psychiatric or neurological disorders. D2 receptor binding was measured by autoradiography in the caudate, putamen and nucleus accumbens, using the specific D2 receptor ligand [3H]-raclopride. In a sample of 44 individuals, only one was homozygous for the A1 allele, 2 5 were homozygous for A2 and 18 were heterozygotes. The presence of one or two A1 alleles was associated with reduced D2 receptor binding in all areas of the striatum, reaching statistical significance in the ventral caudate and putamen (p=0.01 and p=0.044, respectively). This reduction was more marked in males than females, particularly in the putamen. A genetic predisposition to lower D2 receptor expression may increase susceptibility to neuroleptic medication or clinical symptoms that are associated with diseases involving dopaminergic pathology.
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