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 HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 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 HTR2A 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 HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results. CONCLUSION We found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C 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 HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor.

中文翻译：

---

精神分裂症中的 5-羟色胺受体和迟发性运动障碍。

背景迟发性运动障碍(TD)是抗精神病药物治疗的常见副作用。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来研究血清素受体 (HTR) 在调节迟发性运动障碍中的作用。方法 5-羟色胺受体 HTR1A、HTR1B、HTR2A、HTR2C、HTR3A、HTR3B 和 HTR6 基因的 29 个 SNP 在 449 名高加索人（226 名女性和 223 名男性）人群中进行了研究，这些人具有精神分裂症的临床诊断（根据 ICD -10：F20）。由于次要等位基因频率低或未通过 Hardy-Weinberg 平衡检验，排除了五个 SNP。抗精神病药对 5-HT2 受体的亲和力是根据以前的出版物定义的。使用 SEQUENOM 质谱分析仪 4 进行基因分型。结果口面部型TD患者组HTR2A基因rs1928040与TD总诊断等位基因存在统计学显着相关性，基因型呈统计学趋势。此外，在女性组中发现了 HTR2C 的 rs1801412 等位基因和基因型的统计学显着关联。排除分别使用 HTR2A 的患者，HTR2C 拮抗剂对 HTR2A 多态性的关联几乎没有变化，但导致 HTR2C 变体关联幅度的重大变化。由于患者人数较少，这些子分析没有显着的结果。结论 我们发现女性患者中 HTR2A 的 rs1928040 和 X 结合的 HTR2C 的 rs1801412 存在显着相关性。这些关联与 TD 的口面部类型特别相关。排除使用相关拮抗剂的患者特别影响 rs1801412，但不影响 rs1928040 相关关联。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，有必要在更大的未使用 HTR2C 拮抗剂的男性患者中进一步研究 HTR2C 基因的变体。