背景:补体成分C4基因已被鉴定为精神分裂症(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)。此外,C4结构形式的变化可能对C4A和C4B蛋白的脑表达水平有直接或间接的影响。先前的研究已经观察到C4AL与较高的大脑C4A表达和男性和女性之间C4的性别二态性相关。
方法:共招募613例DSM-IV型SCZ或分裂情感障碍(SCZ-AFF)患者,研究C4基因变异与SCZ临床特征(发病年龄,症状严重程度,和全球功能评估(GAF))。本研究还探讨了性别对C4与SCZ相关性的影响。在遗传质量控制后,434例患者被纳入最终分析。
结果:我们观察到C4与SCZ的临床特征(发病年龄,症状严重程度,GAF),并在分别检查男性和女性时发现显着差异。
结论:总体而言,我们的初步发现鼓励未来对SCZ相关表型中C4的研究,包括抗精神病药物反应和副作用。研究样本大小适中;因此,需要在更大的样本中进行进一步的研究来扩展和验证这些结果.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.