Key result
Two novel SNPs of RELN (rs155333 and rs6465938) and a haplotype were nominally associated with antipsychotic treatment response in Chinese Han patients with schizophrenia, though none remained significant after Bonferroni correction.
Why the study?
Individual differences in drug responses are substantial but few prognostic response biomarkers exist, prompting evaluation of whether RELN affects antipsychotics response in the Chinese population.
Do SNPs in the RELN gene affect therapeutic response to antipsychotics in Chinese Han inpatients with schizophrenia?
Observational (n=260)
Single-blind
No
Do SNPs in the RELN gene affect therapeutic response to antipsychotics in Chinese Han inpatients with schizophrenia?
Effect estimate: OR 0.55 (95% CI 0.31-0.99)
p-value: p=0.046
Polymorphisms in the RELN gene, particularly a specific three-SNP haplotype, may be associated with antipsychotic treatment response in the Chinese Han population, though larger validation studies are required.
Nominally associated RELN variants lack robustness after correction; leaves open any predictive role for these SNPs in antipsychotic response pending replication.
Background: There 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. Methods: The 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. Results: Two novel SNPs of RELN [rs155333 (p=0.010) and rs6465938 (p=0.049), but failure multiple correction] were identified to be associated with antipsychotic treatment response. 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). Conclusion: Our 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) remain significant after Bonferroni correction. Therefore, validation is needed in larger pharmacogenetic studies.
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Xu et al. (2020) conducted an observational in Schizophrenia (n=260). Antipsychotics (risperidone, quetiapine, aripiprazole, olanzapine, perphenazine) vs. Different RELN genotypes was evaluated on Antipsychotic treatment response (≥50% reduction in PANSS score) for RELN rs2535764 C/T vs C/C+T/T (OR 0.55, 95% CI 0.31-0.99, p=0.046). Two novel SNPs of RELN (rs155333 and rs6465938) and a haplotype were nominally associated with antipsychotic treatment response in Chinese Han patients with schizophrenia, though none remained significant after Bonferroni correction.
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