Novel 5′-regulatory region polymorphism of the 5ht2c-receptor gene: no association with clozapine-response

The atypical neuroleptic agent clozapine displays a high affinity for various dopamine and serotonin receptors(1), thus making these receptors important candidates for pharmacogenetic studies of response. Recently, two adjacent dinucleotide polymorphisms in the 5′-regulatory region of the X-chromosomal 5-HT2C-receptor gene (2), resulting in length differences (3), have been described. A study by Arranz et al. (4) yielded a positive association between this polymorphism and treatment outcome (measured by the Global Assessment Scale) in 200 clozapine medicated patients. This finding prompted us to analyze whether this effect was present in a previously (5) described sample of 155 German patients treated with clozapine. We performed an association study including 155 German patients who met DSM-IV criteria for schizophrenia (n=142) or schizoaffective disorder (n=13). Patients were grouped according to their response behavior as reported elsewhere (5) Genotyping was carried out according to the protocol of Deckert et al. (6). Five alleles (88 bp, 94 bp, 96 bp, 98 bp, and 100 bp) were observed. There was no difference in allele frequencies and genotype distribution between responders and non-responders. Thus, our results do not support the hypothesis that the overall response to clozapine is associated with variation in the 5-HT2C-receptor gene.