Lack of association between the T→C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia

Mario Masellis, Vincenzo S. Basile, Herbert Y. Meltzer, Jeffrey A. Lieberman, Serge Sevy, David A. Goldman, Mark W. Hamblin, Fabio M. Macciardi, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticle

76 Scopus citations


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: χ2 = 0.06, 1 df, P = 0.80; genotype: χ2 = 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.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalSchizophrenia Research
Issue number1
StatePublished - Jan 15 2001


  • Clozapine response
  • Pharmacogenetic
  • Polymorphism
  • Serotonin receptor

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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