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血清阳性与儿茶酚-O-甲基转移酶 Val105/158Met 变异相互作用增加精神分裂症的风险。

Seropositivity Interacts with Catechol--methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia.

机构信息

Instituto de Neurociencias, Centro de Investigación Biomédica (CIBM), Universidad de Granada, 18016 Granada, Spain.

Departamento de Psiquiatría, Facultad de Medicina, Universidad de Granada, 18016 Granada, Spain.

出版信息

Genes (Basel). 2022 Jun 18;13(6):1088. doi: 10.3390/genes13061088.

Abstract

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case−control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

摘要

精神分裂症是一种异质性和严重的精神病。流行病学研究结果表明,感染弓形虫(Toxoplasma gondii,T. gondii)等病原体与精神分裂症风险增加有关。另一方面,涉及儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)Val105/158Met 多态性的证据表明其与精神分裂症的发病机制有关,因为它改变了多巴胺代谢。对 141 例患者和 142 例对照进行了病例对照研究,以分析多态性、抗 T. gondii IgG 的流行情况及其对精神分裂症风险的相互作用。通过 ELISA 检测 IgG,采用 TaqMan Real-Time PCR 进行基因分型。尽管任何 COMT 基因型与精神分裂症之间都没有关联,但我们发现 T. gondii 血清阳性与该疾病之间存在显著关联(χ2 = 11.71;p 值 < 0.001)。此外,T. gondii 感染引起的精神分裂症风险受到 COMT 基因型的修饰,与未暴露于感染的个体相比,暴露于感染的个体的 COMT 基因型不同,其风险也不同(交互作用的 χ2 = 7.28,p 值 = 0.007)。这项研究提供了证据表明,COMT 基因型修饰了 T. gondii 感染引起的精神分裂症风险,Met/Met 表型个体的风险更高,杂合子个体的风险居中,Val/Val 表型个体的风险较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5df9/9222771/8215f86005d8/genes-13-01088-g001.jpg

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