Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Psychiatry Res. 2018 Jan;259:197-202. doi: 10.1016/j.psychres.2017.10.018. Epub 2017 Oct 7.
Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorders such as bipolar disorder, autism, and schizophrenia in later life. Gamma-butyrobetaine hydroxylase (BBOX 1) is an enzyme responsible for the biosynthesis of l-carnitine, a key molecule in fatty acid metabolism. This cytosolic dimeric protein belongs to the dioxygenase family. In this study, we investigated whether BBOX 1 expression was related to psychiatric disorder in an animal model. We also conducted a case-control study using 284 schizophrenia patients and 409 controls with single-nucleotide polymorphisms (SNPs) in the 5'-near region of BBOX 1. BBOX 1 expression was increased in the medial frontal cortex of a mouse model of schizophrenia induced by maternal immune activation. Furthermore, the genotype and allele frequencies of two SNPs (rs7939644 and rs10767592) were significantly associated with schizophrenia susceptibility. Our results suggest that BBOX 1 might be associated with maternal immune activation and schizophrenia susceptibility. Therefore, it might be involved in the pathophysiology of schizophrenia.
产前暴露于感染或炎症性损伤会增加日后发生神经精神疾病的风险，如双相情感障碍、自闭症和精神分裂症。γ-丁酰甜菜碱羟化酶（BBOX1）是一种负责左旋肉碱生物合成的酶，左旋肉碱是脂肪酸代谢中的关键分子。这种细胞质二聚体蛋白属于加双氧酶家族。在这项研究中，我们研究了 BBOX1 表达是否与动物模型中的精神障碍有关。我们还使用 BBOX1 5'近端区域的单核苷酸多态性（SNP）对 284 名精神分裂症患者和 409 名对照进行了病例对照研究。母体免疫激活诱导的精神分裂症小鼠模型中，内侧前额皮质的 BBOX1 表达增加。此外，两个 SNP（rs7939644 和 rs10767592）的基因型和等位基因频率与精神分裂症易感性显著相关。我们的研究结果表明，BBOX1 可能与母体免疫激活和精神分裂症易感性有关。因此，它可能参与精神分裂症的病理生理学。
