Polymorphisms in dopamine receptors: what do they tell us?

Many genetic studies have focussed on dopamine receptors and their relation ship to neuropsychiatric disease. Schizophrenia, bipolar disorder, and subs tance abuse have been the most studied, but no conclusive linkage or associ ation has been found. The possible influence of dopamine receptor variants on drug response has not received as much attention. While there is some ev idence that polymorphisms and mutations in dopamine receptors can alter fun ctional activity and pharmacological profiles, no conclusive data link thes e gene variants to drug response or disease. The lack of unequivocal findin gs may be related, in part. to the subtle changes in receptor pharmacology that these polymorphisms and mutations mediate. These subtle effects may be obscured by the influence of genes controlling drug metabolism and kinetic s. Further insight into the pharmacogenetics of dopamine receptors may requ ire not just more studies, but novel approaches to the study of complex gen etic traits and,diseases. (C) 2000 Elsevier Science B.V. All rights reserve d.