Alpha-1A adrenergic (ADRA1A) and serotonin 6 (HTR6) receptor gene polymorphisms and clinical response to clozapine

M. Masellis*, V. S. Basile, V. DeLuca, H. Y. Meltzer, J. A. Lieberman, S. G. Potkin, J. L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, 5-HT1A, histamine H1 and a-1A adrenergic receptors has been suggested to contribute to various aspects of its complex clinical actions. The phenotype of clinical response to clozapine is likely to be complex and multifactorial in nature, involving a combination of genetic and environmental factors. This study examined the hypothesis that genetic variation in 5-HT6, histamine H1 and ADRA1A receptor genes is involved in the variability observed in response to clozapine. We tested the hypotheses that antipsychotic response to clozapine is associated with genetic variation in the aforementioned candidate genes. 185 patients with DSM-IIIR diagnosed schizophrenia were prospectively assessed for clinical response to clozapine. c2 tests were utilized to detect differences in candidate gene frequencies among responders and non-responders. We found that there were no significant associations observed for these polymorphisms (ADRA1A: genotype: x2 = 0.55, 2 df, P = 0.76; allele: x2 = 0.21, 1 df, P = 0.64; HTR6: genotype: x2 = 1.21, 2 df, P = 0.55; allele: x2 = 0.06, 1 df, P = 0.8). Our results suggest that these candidates do not contribute to the variability observed in clozapine response, however replication in independent samples is warranted.

Original languageEnglish (US)
Pages (from-to)642
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number7
StatePublished - Oct 8 2001

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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