TY - JOUR
T1 - Lack of association between the T→C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia
AU - Masellis, Mario
AU - Basile, Vincenzo S.
AU - Meltzer, Herbert Y.
AU - Lieberman, Jeffrey A.
AU - Sevy, Serge
AU - Goldman, David A.
AU - Hamblin, Mark W.
AU - Macciardi, Fabio M.
AU - Kennedy, James L.
N1 - Funding Information:
MM was supported by a Department of Psychiatry, Faculty of Medicine, University of Toronto Summer Scholarship. This work was supported by a Medical Research Council of Canada (MT15007) grant and a NARSAD Independent Investigator Award to JLK.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - 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.
AB - 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.
KW - Clozapine response
KW - Pharmacogenetic
KW - Polymorphism
KW - Serotonin receptor
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U2 - 10.1016/S0920-9964(00)00016-5
DO - 10.1016/S0920-9964(00)00016-5
M3 - Article
C2 - 11163544
AN - SCOPUS:0035863032
SN - 0920-9964
VL - 47
SP - 49
EP - 58
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1
ER -
