精神分裂症中的5-羟色胺受体与迟发性运动障碍
5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia.
作者信息
Pozhidaev Ivan V, Paderina Diana Z, Fedorenko Olga Yu, Kornetova Elena G, Semke Arkadiy V, Loonen Anton J M, Bokhan Nikolay A, Wilffert Bob, Ivanova Svetlana A
机构信息
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Department of Cytology and Genetics, National Research Tomsk State University, Tomsk, Russia.
出版信息
Front Mol Neurosci. 2020 Apr 24;13:63. doi: 10.3389/fnmol.2020.00063. eCollection 2020.
BACKGROUND
Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia.
METHODS
A set of 29 SNPs of genes of serotonin receptors , and was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4.
RESULTS
Statistically significant associations of rs1928040 of gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of polymorphisms, but caused a major change of the magnitude of the association of variants. Due to the low patient numbers, these sub-analyses did not have significant results.
CONCLUSION
We found significant associations in rs1928040 of and for rs1801412 of X-bound in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the gene in a larger group of male patients who were not using antagonists is necessary in order to verify a possible functional role of this receptor.
背景
迟发性运动障碍（TD）是抗精神病药物治疗常见的副作用。这种运动障碍由口面部和肢体-躯干部分组成。本研究旨在通过对精神分裂症患者进行基因分型，研究5-羟色胺受体（HTR）在调节迟发性运动障碍中的作用。
方法
在449名经临床确诊为精神分裂症（根据ICD-10：F20）的白种人（226名女性和223名男性）群体中，研究了一组5-羟色胺受体基因的29个单核苷酸多态性（SNP）。由于次要等位基因频率较低或未通过哈迪-温伯格平衡检验，排除了5个SNP。根据先前的出版物确定抗精神病药物与5-HT2受体的亲和力。使用SEQUENOM Mass Array Analyzer 4进行基因分型。
结果
在口面部型TD患者组和TD总诊断组中，发现基因rs1928040的等位基因存在统计学显著关联，基因型存在统计学趋势。此外，在女性组中发现基因rs1801412的等位基因和基因型存在统计学显著关联。分别排除使用HTR2A、HTR2C拮抗剂的患者后，多态性的关联变化不大，但导致基因变异关联程度的重大变化。由于患者数量较少，这些亚分析没有显著结果。
结论
我们在女性患者中发现基因rs1928040和X连锁基因rs1801412存在显著关联。这些关联尤其与口面部型TD有关。排除使用相关拮抗剂的患者对rs1801412的影响尤为明显，但对rs1928040相关关联没有影响。这表明rs1801412与HTR2C的功能直接或间接相关。为了验证该受体可能的功能作用，有必要在更大规模的未使用拮抗剂的男性患者群体中进一步研究该基因的变异。
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