Expression and characterization of a dopamine D4R variant associated with delusional disorder
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M T Zenner1, M Nobile, R Henningsen
1Hoffmann-La Roche, Pharmaceutical Research, Preclinical Neuroscience, Basel, Switzerland.
Abstract:
Multiple genetic polymorphisms of the human dopamine D4 receptor (hD4R) have been identified including a 12 bp repeat in exon 1 associated with a psychotic condition called delusional disorder. Competition binding assays revealed minor pharmacological differences between the recombinant A1 (normal) and A2 (delusional) proteins with respect to quinpirole and the antipsychotic clozapine, however no functional differences were detected for receptor activation by dopamine, epinephrine, or norepinephrine. Our results suggest that this polymorphism may only confer susceptibility to delusional disorder in combination with other genetic or environmental factors.
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