Lack of association between the T -> C 267 serotonin 5-MT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia

The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A rece ptors has been suggested to contribute to various aspects of its complex cl inical actions. This study examined the hypothesis that genetic variation i n 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability ob served in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well ch aracterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-MT 1A (HTR6) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for e ither an allelic or genotypic association of the T-->C 267 HTR6 polymorphis m with response to clozapine was found in our sample (allele: chi (2)=0.06, 1 df, P=0.80; genotype: chi (2)=1.21. 2 df, P=0.55), The pro161eu HTR1A po lymorphism was not observed in our sample: all individuals genotyped were p ro/pro 16 homozygotes, With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro /leu 279 genotype), This individual was clinically similar to the other clo zapine responders. Overall, our findings do not support a role for the T--> C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, alt hough replication is required to confirm this finding. (C) 2001 Elsevier Sc ience B.V. All rights reserved.