Abstract
BackgroundThere are great individual differences in the drug responses; however, there are few prognostic drug response biomarkers available. RELN is one of the more extensively examined schizophrenia candidate genes. The purpose of this study was to determine whether RELN can affect antipsychotics response in the Chinese population. This may lead to the discovery of relevant novel drug response markers.MethodsThe unrelated 260 Chinese Han inpatients with schizophrenia were enrolled in the present study. The enrolled subjects have been prescribed antipsychotic medication during the study. A total of 15 SNPs of RELN were genotyped by MassARRAY® platform. The association of the RELN gene with therapeutic response to antipsychotics was analyzed based on sex and age at onset.ResultsTwo novel SNPs of RELN were found to be associated with antipsychotic treatment response (rs155333, p = 0.010 and rs6465938, p = 0.049) at nominal significance threshold, but not after multiple correction. Our study also revealed highly significant association of a haplotype consisting of three SNPs (rs362814-rs362626-rs2237628) with antipsychotic treatment response. Even after permutation, the p-value indicated significant association (rs362814-rs362626-rs2237628: ACT, χ2 = 6.353, p = 0.0117, permuted p = 0.04). Furthermore, a novel SNP, rs2535764, was found to be associated with antipsychotic response under overdominant genetic model at a marginal significant level of 0.046 (C/T vs. C/C + T/T: p = 0.046, AIC = 314.7, BIC = 321.6).ConclusionOur data indicated that RELN can affect antipsychotic treatment outcomes in the Chinese population. SNPs of RELN could be used as predictive biomarkers for future personalized medicine of antipsychotic drug treatment. However, none of the three novel SNPs (rs155333, rs6465938, and rs2535764) remained significant after Bonferroni correction. Therefore, validation is needed in larger pharmacogenetic studies.
Highlights
Schizophrenia is a widespread mental disorder with periods of remission and relapses over a patient’s lifetime (van Os and Kapur, 2009; Jann and Penzak, 2018), and long-term treatment with antipsychotic drugs is often required (Kahn et al, 2015)
In order to assess whether duration of the disorder would influence patients’ response to the antipsychotic drugs, we applied univariate general linear model to assess the association with response to the antipsychotic treatment
In order to control this confounding factor, we applied general linear model setting age as a covariate to assess the association of genotype with antipsychotic treatment response (PANSS percentage change) in the subsequent analysis
Summary
Schizophrenia is a widespread mental disorder with periods of remission and relapses over a patient’s lifetime (van Os and Kapur, 2009; Jann and Penzak, 2018), and long-term treatment with antipsychotic drugs is often required (Kahn et al, 2015). There are great individual differences in antipsychotic drug treatment responses, in terms of both therapeutic effects and adverse effects (Xu et al, 2013). More exploratory studies that investigate other genes of interest likely represent a superior strategy for discovering relevant novel antipsychotic drug response markers. These newly discovered antipsychotic treatment markers have the potential to be novel drug targets for schizophrenia. The purpose of this study was to determine whether RELN can affect antipsychotics response in the Chinese population This may lead to the discovery of relevant novel drug response markers
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