ABSTRACT
Second-generation antipsychotics (SGAs) play a critical role in current treatment of schizophrenia (SCZ). It has been observed that sinus bradycardia, rare but in certain situations life threatening adverse drug reaction, can be induced by SGAs across different schizophrenia populations. However, the roles of genetic factors in this phenomenon have not been studied yet. In the present study, a genome-wide association study of single nucleotide polymorphisms (SNPs) was performed on Chinese Han SCZ patients to identify susceptibility loci that were associated with sinus bradycardia induced by SGAs. This study applied microarray to obtain genotype profiles of 88 Han Chinese SCZ patients. Our results found that there were no SNPs had genome-wide significant association with sinus bradycardia induced by SGAs. The top GWAS hit located in gene KIAA0247, which mainly regulated by the tumor suppressor P53 and thus plays a role in carcinogenesis based on resent research and it should not be a susceptibility locus to sinus bradycardia induced by SGAs. Using gene-set functional analysis, we tested that if top 500 SNPs mapped genes were relevant to sinus bradycardia. The result of gene prioritization analysis showed CTNNA3 was strongly correlated with sinus bradycardia, hinting it was a susceptibility gene of this ADR. Our study provides a preliminary study of genetic variants associated with sinus bradycardia induced by SGAs in Han Chinese SCZ patients. The discovery of a possible susceptibility gene shed light on further study of this adverse drug reaction in Han Chinese SCZ patients.
Subject(s)
Antipsychotic Agents/adverse effects , Bradycardia/etiology , Genome-Wide Association Study , Schizophrenia/genetics , Adult , Antipsychotic Agents/therapeutic use , Bradycardia/genetics , China , Female , Genotype , Humans , Male , Membrane Proteins/genetics , Middle Aged , Polymorphism, Single Nucleotide , Protein Interaction Maps/genetics , Schizophrenia/drug therapy , Schizophrenia/pathology , Tumor Suppressor Protein p53/metabolism , alpha Catenin/geneticsABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of risperidone versus traditional agents in treating Tourette's syndrome. METHODS: Randomized, controlled trials (RCTs) of risperidone versus traditional agents for Tourette's syndrome were identified, and eligible studies were included according to our established strategy. Besides methodological quality of inclusive trials, assessed by the Jadad scale, heterogeneity test, Meta-analysis, funnel plot analysis, subgroup analysis and sensitivity analysis were used to analyze the data. RESULTS: A total of 12 RCTs were included, with most trials of low methodological quality and high heterogeneity. Meta-analysis from 11 of the identified RCTs, involving total 741 patients, showed that there was no significant difference in efficacy between risperidone and traditional agents, based on the results of sensitivity analysis, and analyses of a haloperidol subgroup and a domesticforeign subgroup. The funnel plots was approximately symmetrical, indicating little publication bias. Risperidone presented mild side effects overall, including extrapyramidal symptoms (EPS), autonomic nervous system symptoms, toxic reactions and the Treatment Emergent Symptom Scale (TESS) score of the treatment group were significantly less than those of control. CONCLUSION: Risperidone appears to have the same efficacy and appropriate safety as traditional agents in treating Tourette's syndrome. Because of the low validity of the results, we are searching for support from the more RCTs with higher methodological quality.
