Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Schizophr Res. 2024 Sep;271:309-318. doi: 10.1016/j.schres.2024.07.039. Epub 2024 Jul 30.
The complement component C4 gene has been identified as a strong marker for schizophrenia (SCZ) risk. The C4 gene has a complex genetic structure consisting of variable structural elements (C4A, C4B, C4L, and C4S) and compound structural forms (C4AL, C4BL, C4AS and C4BS). In addition, the variations in C4 structural forms may have a direct or indirect effect on the brain expression level of C4A and C4B proteins. Previous studies have associated C4AL with higher brain C4A expression and sex-dimorphism of C4 between males and females was observed.
A total of 613 patients with DSM-IV SCZ or schizoaffective disorder (SCZ-AFF) were recruited to investigate the relationship between C4 gene variants and clinical characteristics of SCZ (age of onset, symptom severity, and global assessment of functioning (GAF)). This study also explored the effect of sex on the association of C4 with SCZ. 434 patients were included in the final analyses after genetic quality control.
We observed associations between C4 and clinical characteristics of SCZ (age of onset, symptom severity, GAF) and found significant differences when males and females were examined separately.
Overall, our preliminary findings encourage future investigations of C4 in SCZ-related phenotypes, including antipsychotic response and side effects. The study sample was of moderate size; therefore, further studies in larger samples are needed to extend and validate these results.
补体成分 C4 基因已被确定为精神分裂症（SCZ）风险的强标志物。C4 基因具有复杂的遗传结构，由可变结构元件（C4A、C4B、C4L 和 C4S）和复合结构形式（C4AL、C4BL、C4AS 和 C4BS）组成。此外，C4 结构形式的变化可能直接或间接地影响 C4A 和 C4B 蛋白在大脑中的表达水平。先前的研究表明 C4AL 与大脑中 C4A 的表达水平较高有关，并且在男性和女性之间观察到 C4 的性别二态性。
共招募了 613 名符合 DSM-IV 精神分裂症或分裂情感障碍（SCZ-AFF）标准的患者，以研究 C4 基因变异与精神分裂症（发病年龄、症状严重程度和全球功能评估（GAF））的临床特征之间的关系。本研究还探讨了性别对 C4 与精神分裂症之间关联的影响。经过遗传质量控制，最终有 434 名患者纳入了最终分析。
我们观察到 C4 与精神分裂症的临床特征（发病年龄、症状严重程度、GAF）之间存在关联，并且当分别检查男性和女性时，发现了显著差异。
总体而言，我们的初步发现鼓励未来对 C4 在与精神分裂症相关表型中的作用进行研究，包括抗精神病药物反应和副作用。研究样本规模适中；因此，需要在更大的样本中进一步研究以扩展和验证这些结果。
