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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00177

Genetic association of olanzapine treatment response in Han Chinese schizophrenia patients

 Shengying Qin1, 2*,  Wei Zhou2,  Yong Xu3,  Qinyu Lv4, Yong-hui Sheng5, Mo Li2, Lu Shen2,  Cong Huai2,  Zhenghui Yi4* and  Donghong Cui6*
  • 1Shanghai Jiao Tong University, China
  • 2Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, China
  • 3First Hospital of Shanxi Medical University, China
  • 4Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University, China
  • 5Shandong Mental Health Center, China
  • 6Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, China

Olanzapine is a second-generation antipsychotic medication, which plays a predominant role in current treatment of schizophrenia. It has been observed that the olanzapine response in schizophrenia treatment is different across individuals. However, predicting such individual-specific olanzapine response requires deep understanding of relevant biomarkers. Here, we performed an integrative investigation on 238 Han Chinese schizophrenia patients, aiming to identifying hidden predictive biomarkers that were related to the efficacy of olanzapine treatment. 143 genes were sequenced from 79 Han Chinese schizophrenia patients using HaloPlex technology. The following analysis indicated that there were 12 single nucleotide polymorphisms (SNPs) were significantly associated with drug response of olanzapine. These novel SNPs were verified in 159 other patients (independent cohort) as well as in the overall 238 patients that were composed of two cohorts we used in this study using MassARRAY platform. The results showed that 2 SNPs were associated with the olanzapine response in both independent cohort (rs324026, P = 0.023 and rs12610827, P = 0.043, respectively) and total cohort (rs324026, adjust P = 0.014 and rs12610827, adjust P = 0.012, respectively). This study provides systematic analyses of genetic variants that were associated with olanzapine responses in Han Chinese schizophrenic patients. Our discovery of genetic biomarkers in olanzapine-response will shed light on future personalize olanzapine treatment design for Han Chinese schizophrenic patients.

Keywords: olanzapine, polymorphism, Schizophrenia, biomarker, association study

Received: 03 Sep 2018; Accepted: 11 Feb 2019.

Edited by:

Amit V. Pandey, University of Bern, Switzerland

Reviewed by:

Julio Benitez, Universidad de Extremadura, Spain
Ming Ta Michael Lee, Geisinger Health System, United States
Vindhya Udhane, Medical College of Wisconsin, United States  

Copyright: © 2019 Qin, Zhou, Xu, Lv, Sheng, Li, Shen, Huai, Yi and Cui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Shengying Qin, Shanghai Jiao Tong University, Shanghai, China, chinsir@sjtu.edu.cn
Dr. Zhenghui Yi, Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Xuhui, ICP 05227, Shanghai, China, yizhenghui1971@163.com
Dr. Donghong Cui, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, 201108, China, manyucc@126.com