ASSOCIATION BETWEEN CLOZAPINE RESPONSE AND ALLELIC VARIATION IN THE 5-HT2C RECEPTOR GENE

A cysteine to serine substitution at amino acid 23 in the 5-HT2C recep tor gene alters the pharmacological properties of the protein. We inve stigated this polymorphism in subjects with schizophrenia resistant to conventional neuroleptic drugs, and analysed our data for allelic ass ociation between the disease state or clinical response to the atypica l antipsychotic drug, clozapine. Ninety percent of subjects who had on e or more 5-HT(2C)ser alleles (19/21) were classified as clozapine res ponders compared with 59% (84/141) without this allele (chi(2) = 7.7, p = 0.005), suggesting that this mutation is a predictor of good respo nse to clozapine. There was no association between schizophrenia and t he 5-HT(2C)ser allele, but our results indicate that the 5-HT2C recept or may contain the major site of action through which clozapine mediat es its antipsychotic effects.