Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone

Abstract

Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A À1438G4A, 102T4C, H452Y; DRD2 À141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n¼25), PANSS total scores of patients with Ins-A2/ Del-A1 diplotype (n¼10) showed 40% greater improvement (P¼0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n¼22) tended to show 15% worse improvement compared with A-T/G-C diplotype (n¼33) (P¼0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.

Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment

“…Nevertheless, two other studies did not report a significant contribution of the Val 158 Met polymorphism of the COMT gene to schizophrenia and concluded that either the Val allele is in linkage disequilibrium (LD) with a nearby causal marker or the results differ when ethnically different populations are considered or the risk conferred by the Val allele is extremely low. 12,13 Results have also been obtained that suggest an eventual influence of this polymorphism in the response of schizophrenic patients to typical 14 and atypical 15 neuroleptics.…”

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

“…In all, 22 SNPs were selected on the basis of prior knowledge of their involvement with response to risperidone or to other antipsychotic drugs. The selected SNPs and genes included ANKK1 (rs1800497 [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Genotyping was performed by Cogenics (Newton, MA, USA) using Sequenom MassARRAY iPlex as previously described. 20 Statistical analysis African-American and white patients who had received at least one dose of risperidone between week 0 and study end (week 12) and who had consented to DNA testing were included in the analysis.…”

“…In the current study, we present results from an analysis of the association between antipsychotic response and 22 single-nucleotide polymorphisms (SNPs), earlier reported to be associated with antipsychotic response, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] using data from a randomized, double-blind study of early response to a single drug (risperidone) in patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. 18 The majority of patients in the trial were African-American and white adults, the former being a group that has been underrepresented in pharmacogenomic studies.…”

Association Studies of DRD2 and COMT Gene Polymorphisms with Risperidone-induced Amenorrhea in Female Schizophrenia Patients

“…Rs6277 had association with plasma prolactin increasing and schizophrenia in the study of different populations, which is also one of susceptible locus in Chinese Han population schizophrenia patients [21][22][23]. A DRD2 haplotype (-141delC and TaqIA) tended to correlate with better clinical performance of risperidone in Japanese schizophrenia patients [24]. Moreover, patients with DRD2-141C Ins/Del polymorphism had a better treatment with risperidone.…”