SEROTONIN SUBTYPE-2 RECEPTOR GENES AND CLINICAL-RESPONSE TO CLOZAPINEIN SCHIZOPHRENIA-PATIENTS

Using a pharmacogenetic approach in 185 schizophrenics who have been p rospectively assessed for clozapine response, we have examined the hyp othesis that polymorphisms if? the 5-HT2A (HTR2A), and 5-HT2C (HTR2C) genes are involved in its variable response. A-1438 A-->G polymorphism in the putative promoter and a silent T-->C 102 substitution in HTR2A were in almost complete linkage disequilibrium, and neither was assoc iated with response (T-->C 102 allele: chi(2) = 0.02; 1 df, p = .90; g enotype: chi(2) = 0.02, 2 df,p = .99). A his452tyr HTR2A polymorphism was found to be associated with clozapine response (his452tyr allele: chi(2) = 6.43, 1 df,p = .01 [p = .04, Bonferroni corrected]; genotype: chi(2) = 6.54, 2 df,p = .04 [p = .16, Bonferroni corrected]). No HTR2 A haplotype was associated with response. Interethnic differences were observed in frequencies of tie cys23ser HTR2C polymorphism. This poly morphism seas not significantly associated with response in either of the ethnic groups (Caucasian and African American genotype: chi(2) = 3 .46, 2 df,p = .18; chi(2) = .31, 2 df,p = .86, respectively). Although replication is required, thee over all results suggest that the his45 2tyr HTR2A polymorphism may be involved in clozapine response. (C) 199 8 American College of Neuropsychopharmacology. Published by Elsevier S cience Inc.