Original Research ARTICLE
Human Aquaporin 4 Gene Polymorphisms and Haplotypes are Associated with Serum S100B Level and Negative Symptoms of Schizophrenia in a Southern Chinese Han Population
- 1Tri-Service General Hospital, Taiwan
- 2National Defense Medical Center, Taiwan
- 3Calo Psychiatric Center, Taiwan
Background: Aquaporin 4 (AQP4) polymorphism may influence the required dosage of antipsychotic drugs. However, the roles of AQP4 polymorphisms in the blood–brain barrier and different neuroprotective effects need further exploration. This study aims to investigate whether the gene polymorphisms and haplotype of AQP4 are associated with serum S100 calcium-binding protein B (S100B) level and clinical symptoms in patients with schizophrenia (SCZ).
Methods: We recruited 190 patients with SCZ. They provided demographic data, completed relevant questionnaires, and submitted samples to test for four AQP4 tag single nucleotide polymorphisms (SNPs) and eight haplotypes. The rating scales of Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP), the Global Assessment of Functioning (GAF), Clinical Global Impression (CGI) were assessed and serum S100B level were measured repeatedly during antipsychotic treatment at weeks 0 (baseline), 3, 6 and 9. Using generalized estimating equation (GEE) analyses, log-transformed S100B (logS100B) level was tested for associations with haplotype and other dependent variables.
Results: Discretization via the median split procedure showed that logS100B level >1.78 or <1.78 had the best discriminant validity to stratify the patients into two groups. After 9 weeks of treatment, the serum S100B level was decreased. The TAA haplotype of AQP4 SNPs was associated with increased serum S100B level (p =.006). The PANSS negative subscale (PANSS-N) (p =.001) and Clinical Global Impression–Improvement (CGI-I) (p =.003) scores had a positive association with S100B level.
Conclusion: Patients with the TAA haplotype of the AQP4 polymorphism are likely to have increased serum S100B level, negative symptoms and poor control of neuroinflammation. A logS100B level >1.78 may be sufficiently specific to predict a higher severity of negative symptoms. Further study including healthy controls and patients with first and recurrent episodes under selective AQP4 modulators will be necessary to explore the profound effects on the treatment of patients with SCZ and may positively inﬂuence their overall outcome.
Keywords: Schizophrenia (SCZ), Aquaporin 4 (AQP4), single nucleotide polymorphism (SNP), haplotype, S100 calcium-binding protein B (S100B)
Received: 18 Jul 2018;
Accepted: 19 Nov 2018.
Edited by:Weihua Yue, Peking University Sixth Hospital, China
Reviewed by:Yong Xu, First Hospital of Shanxi Medical University, China
Jianping Zhang, Zucker Hillside Hospital, United States
Copyright: © 2018 Wu, Sytwu and Lung. 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.
Prof. Huey-Kang Sytwu, National Defense Medical Center, Taipei, 114, Taiwan, email@example.com
Prof. For-Wey Lung, Calo Psychiatric Center, Pingtung County, Taiwan, firstname.lastname@example.org