| 1 | Schizophr. Res. 2001 Jan 47: 49-58 |
|---|---|
| PMID | 11163544 |
| Title | Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. |
| Abstract | 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) ofschizophreniapatients 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: chi(2)=0.06, 1 df, P=0.80; genotype: chi(2)=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 pro279leuHTR7polymorphism, 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. |
| SCZ Keywords | schizophrenia |
| 2 | Neuropsychopharmacology 2006 Apr 31: 866-71 |
| PMID | 16192982 |
| Title | Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population. |
| Abstract | Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology ofschizophrenia. The 5-HT7 receptor is considered to be a possibleschizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT7 receptor gene (HTR7) and selected four 'haplotype-tagging (ht) SNPs'. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japaneseschizophreniapatients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated withschizophrenia. A promoter SNP (SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function ofHTR7, our results support the supposition thatHTR7is a susceptibility gene forschizophreniain this ethnic group. |
| SCZ Keywords | schizophrenia |
| 3 | Pharmacogenomics 2008 Oct 9: 1437-43 |
| PMID | 18855532 |
| Title | 多巴胺和5 -羟色胺候选基因的变异as predictors of response to risperidone treatment in first-episode schizophrenia. |
| Abstract | Abnormalities in dopaminergic and serotonergic transmission systems are thought to be involved in the pathophysiology ofschizophreniaand the mechanisms underlying the therapeutic effects of antipsychotics. We conducted a pharmacogenetic study to evaluate whether variants in dopamine-related genes (DRD1-DRD5, AKT1 and GSK3beta) and serotonin receptor genes (HTR1A, HTR1B, HTR1D, HTR2A, HTR2C, HTR6 andHTR7) can be used to predict the efficacy of risperidone treatment forschizophrenia. 总共有120-episode neuroleptic-naiveschizophreniapatients were treated with risperidone monotherapy for 8 weeks and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale. Among the 30 variants that we examined, two SNPs in DRD2 (-241A>G [rs1799978] and TaqIA [rs1800497]) and two SNPs in AKT1 (AKT1-SNP1 [rs3803300] and AKT1-SNP5 [rs2494732]) were significant predictors of treatment response to risperidone. These data suggest that the SNPs in DRD2 and AKT1 may influence the treatment response to risperidone inschizophreniapatients. |
| SCZ Keywords | schizophrenia |
| 4 | Mol. Psychiatry 2009 Aug 14: 804-19 |
| PMID | 18521090 |
| Title | Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study. |
| Abstract | A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients withschizophrenia. Genotypes of 407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene (NPAS3), close to a translocation breakpoint site previously observed in a family withschizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene (XKR4), the tenascin-R gene (TNR), the glutamate receptor, inotropic, AMPA 4 gene (GRIA4), the glial cell line-derived neurotrophic factor receptor-alpha2 gene (GFRA2), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene (HTR7). The study of these polymorphisms and genes may lead to a better understanding of the etiology ofschizophreniaand of its treatment. These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio. |
| SCZ Keywords | schizophrenia |
| 5 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 547-51 |
| PMID | 19233240 |
| Title | Association analysis of serotonin receptor 7 gene (HTR7) and risperidone response in Chinese schizophrenia patients. |
| Abstract | Several lines of evidence suggest that the human 5-HT(7) receptor may be involved in the pharmacodynamics of risperidone and may influence clinical response of the drug. A pharmocogenetics study of this receptor may therefore be useful in developing individualized therapy. But few studies about it have been done. In this study, we genotyped ten single nucleotide polymorphisms (SNPs) distributed throughout theHTR7gene and analyzed six of them for association with the reduction of Brief Psychiatric Rating Scale (BPRS) scores in drug-naive Chineseschizophreniapatients, following an eight-week period of risperidone monotherapy. The confounding effects of nongenetic factors were estimated and the baseline symptom score as well as the duration of illness were included as covariates for adjustment. No significant correlation ofHTR7with antipsychotic efficacy was detected in either genotype or haplotype analysis. These results demonstrate that variations in theHTR7gene may not be good genetic markers for predicting the therapeutic efficacy of risperidone. |
| SCZ Keywords | schizophrenia |
| 6 | Neuropsychobiology 2015 -1 72: 118-25 |
| PMID | 26609891 |
| Title | Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients. |
| Abstract | Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japaneseschizophrenia. Perospirone or aripiprazole was administered to 100 patients withschizophreniain a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). Our results show thatHTR7variants are not related to the overall improvement inschizophreniasymptoms. |
| SCZ Keywords | schizophrenia |