title: Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia.
abstract: The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism 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 pro16leu HTR1A polymorphism was not observed in our sample; all individuals genotyped were pro/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 clozapine 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, although replication is required to confirm this finding.
authors.affiliation: Neurogenetics Section, Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Ontario M5T 1R8, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Masellis
authors.forename: V S
authors.initials: VS
authors.lastname: Basile
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: J A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: S
authors.initials: S
authors.lastname: Sevy
authors.forename: D A
authors.initials: DA
authors.lastname: Goldman
authors.forename: M W
authors.initials: MW
authors.lastname: Hamblin
authors.forename: F M
authors.initials: FM
authors.lastname: Macciardi
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D003024:Clozapine