Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia.
Earlier results suggest a minor role of variants in the serotonin 3 receptor (HTR3) subunit genes on antipsychotic treatment outcome of schizophrenia patients. In this study, we further investigated the role of the subunits A and B of the HTR3 receptor using 140 schizophrenia patients taking clozapine for 6 months. We have found significant allelic association of clozapine response with three variants in the HTR3A receptor (rs2276302, rs1062613, rs1150226) although only rs1062613 association remained significant after permutations (permutated P=0.041). Moreover, rs2276302 and rs1062613 have shown nominally significant genotypic association. The two haplotypes composed of rs2276302-rs1062613-rs1150226 were also nominally significant. Taken together, our results suggest that variants in the HTR3A receptor gene can play a role in the treatment outcome of clozapine in schizophrenia patients that are refractory or intolerant of typical antipsychotic therapy. Further studies are necessary to confirm the reported associations.
Souza
Renan P
RP
Neurogenetics Section, Department of Neuroscience, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada. renanrps@yahoo.com.br
de Luca
Vincenzo
V
Meltzer
Herbert Y
HY
Lieberman
Jeffrey A
JA
Kennedy
James L
JL
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; C509409:HTR3A protein, human; C509410:HTR3B protein, human; D044406:Receptors, Serotonin, 5-HT3; D003024:Clozapine