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

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00633

Association Study of KCNH7 Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia

 Xueping Wang1, 2,  Yi Su1, 2, Hao Yan1, 2, Zhuo Huang3, 4,  Yu Huang5* and  Weihua Yue1, 2*
  • 1Peking University Sixth Hospital, China
  • 2Key Laboratory of Mental Health, Ministry of Health, Peking University, China
  • 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, China
  • 4Key Laboratory for Neuroscience, Ministry of Education / National Health and Family Planning Commission, Peking University, China
  • 5Peking University, China

Risperidone has been used to treat the symptoms of schizophrenia and reduce its relapse. However, the responses to treatment show great variability among patients. The potassium channel has been reported as an effective target for antipsychotics. KCNH7, a member of the voltage-gated K+ channel Kv11 family, is primarily expressed in the brain. Here, we assessed the genetic association of KCNH7 with risperidone responses in 393 schizophrenia patients. The patients were treated with risperidone for six weeks. The reduction rates of Positive and Negative Syndrome Scale (PANSS) scores were determined to quantify drug response. We also examined the associations between six single-nucleotide polymorphisms (SNPs) of KCNH7 and the risperidone responses for a total of six weeks. The SNP rs77699177 (C>T) in the KCNH7 gene intron was significantly associated with the treatment response reflected by the PANSS reduction rate (CC, 55.8 ± 23.0; TC, 70.9 ± 20.3, P = 0.000110), indicating that patients with the TC genotype have better efficacy for antipsychotic therapy. The rs2241240 SNP also showed a significant association with treatment responses after 6 weeks of treatment (P = 0.00256). The findings indicate that the voltage-gated K+ channel KCNH7 is a potential functional marker for the identification of the response to risperidone treatment in schizophrenia patients.

Keywords: Schizophrenia, risperidone medications, KCNH7, Treatment responses, pharmacogenomics

Received: 03 Nov 2018; Accepted: 06 Aug 2019.

Copyright: © 2019 Wang, Su, Yan, Huang, Huang and Yue. 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:
PhD. Yu Huang, Peking University, Beijing, 100871, Beijing Municipality, China, hy@pku.edu.cn
MD. Weihua Yue, Peking University Sixth Hospital, Beijing, 100191, Beijing Municipality, China, dryue@bjmu.edu.cn