AUTHOR=Xu Qingqing , Li Mo , Qin Shengying , Li Yaojing , Ning Ailing , Fu Yingmei , Wang Dongxiang , Zeng Duan , Li Huafang , Yu Wenjuan , Yu Shunying 

TITLE=Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00007

DOI=10.3389/fphar.2020.00007

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>There are great individual differences in the drug responses; however, there are few prognostic drug response biomarkers available. <italic>RELN</italic> is one of the more extensively examined schizophrenia candidate genes. The purpose of this study was to determine whether <italic>RELN</italic> can affect antipsychotics response in the Chinese population. This may lead to the discovery of relevant novel drug response markers.</p></sec><sec><title>Methods</title><p>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 <italic>RELN</italic> were genotyped by MassARRAY<sup>®</sup> platform. The association of the <italic>RELN</italic> gene with therapeutic response to antipsychotics was analyzed based on sex and age at onset.</p></sec><sec><title>Results</title><p>Two novel SNPs of <italic>RELN</italic> 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 <italic>p</italic>-value indicated significant association (rs362814-rs362626-rs2237628: ACT, χ<sup>2</sup> = 6.353, <italic>p</italic> = 0.0117, permuted <italic>p</italic> = 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: <italic>p</italic> = 0.046, AIC = 314.7, BIC = 321.6).</p></sec><sec><title>Conclusion</title><p>Our data indicated that <italic>RELN</italic> can affect antipsychotic treatment outcomes in the Chinese population. SNPs of <italic>RELN</italic> 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.</p></sec>