Association Study of the Complement Component C4 Gene in Tardive Dyskinesia.

Clement C Zai,Sajid A Shaikh,Daniel J Müller,Deanna Herbert,Gary Remington,Gwyneth C Zai,Jennie G Pouget,Nicole Braganza,Sheraz Y Cheema,Heather Emmerson,Maria Tampakeras,Arun K Tiwari,James Greco,James L Kennedy,Natalie Freeman,Aristotle N Voineskos

doi:10.3389/fphar.2019.01339

Clement C Zai, Sajid A Shaikh + Show 14 more

Open Access

https://doi.org/10.3389/fphar.2019.01339

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Abstract

Tardive dyskinesia (TD) is a movement disorder that may develop in schizophrenia patients being treated long-term with antipsychotic medication. TD interferes with voluntary movements and leads to stigma, and can be associated with treatment non-adherence. The etiology of TD is unclear, but it appears to have a genetic component. There is emerging evidence of immune dysregulation in TD. In the current study, we set out to investigate the complex schizophrenia-associated complement component 4 (C4) gene for possible association with TD occurrence and TD severity as assessed by the Abnormal Involuntary Movement Scale (AIMS) in a sample of 129 schizophrenia patients of European ancestry. We have genotyped the copy numbers of long and short forms of C4A and C4B gene variants in 129 European ancestry patients with schizophrenia or schizoaffective disorder. We did not find predicted C4A or C4B expression to be nominally associated with TD risk or severity. However, we found the number of copies of C4BL to be nominally associated with TD severity (p = 0.020).

Highlights

Schizophrenia is a chronic and severe psychiatric disorder characterized by, amongst other symptoms, hallucinations and delusions
This is the first study to examine the component 4 (C4) gene in Tardive dyskinesia (TD), and we found a possible association between C4BL copy number and TD severity
It is important to note that due to the exploratory nature of our study, we did not correct for multiple testing, and our findings with copy number of C4BL would not have survived Bonferroni correction

Summary

Introduction

Schizophrenia is a chronic and severe psychiatric disorder characterized by, amongst other symptoms, hallucinations and delusions. Its etiology is complex and remains unclear, but immunerelated mechanisms have been postulated (Khandaker and Dantzer, 2016; van Kesteren et al, 2017). In 2009, two genome-wide association studies implicated the major histocompatibility complex (MHC) region in schizophrenia (Shi et al, 2009; Stefansson et al, 2009). Symptoms of schizophrenia are treated with antipsychotics, which, as a medication class, is associated with risk of developing tardive dyskinesia (TD). The etiology of TD remains unclear (Lee and Kang, 2011; Zai et al, 2018a; Zai et al, 2018b), but a genetic component has been supported by family studies (Weinhold et al, 1981; Yassa and Ananth, 1981; Müller et al, 2001)

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