Efficacy and side-effects of clozapine: Testing for association with allelic variation in the dopamine D-4 receptor gene

Genetic factors are supposed to play a major role not only in the etiology of psychiatric disorders but also in individual response to medications. To test the hypothesis that interindividual differences in response to clozapine and the occurrence of side-effects might be influenced by variations in the dopamine D-4 receptor gene, we examined frequencies of four known polymorphic sites affecting protein structure in the dopamine D-4 receptor gene in 149 patients with schizophrenia or schizoaffective disorder treated with clozapine. The D-4 polymorphisms included a 13-base pair deletion, which through a frameshift leads to a truncated nonfunctional receptor protein. There were, however, no significant differences in genotype counts between responders and non-responders. Furthermore, no side-effect was found to be associated with genetic variants of the dopamine D-4 receptor. (C) 1996 American College of Neuropsychopharmacology