Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response

Dopamine receptors are strong candidates for involvement in schizophrenia and are targeted by a wide variety of antipsychotics, We hypothesized that genetic variation in these neurotransmitter receptors may influence clinical response to clozapine, an antipsychotic which displays high affinity for dopamine D2 receptors in the limbic system. To test this hypothesis, we studied a functional polymorphism in the promoter region of the D2 receptor gene (-141C Ins/Del) in a sample of 151 clozapine treated patients of British origin, In addition, the influence of this polymorphism on antipsychotic response in general was investigated on a sample of 146 Dan Chinese schizophrenic patients treated with a variety of antipsychotics, No association was found between this polymorphism and clinical response in either of the two samples suggesting that genetic variation in D2 receptors does not play a major role in determining clinical response to antipsychotic treatment. Pharmacogenetics 8:481-484. (C) 1998 Lippincott Williams & Wilkins.