血清素接受體及運送基因多型性與慢性精神分裂症病患之遲發性運動異常之相關性研究

Abstract

背景與目標：遲發性運動異常 (Tardive dyskinesia, TD)，是抗精神病藥物副作用中較嚴重的一種。TD的病理機轉目前並未完全了解，有研究指出與血清素基因有關。本研究目的為探討血清素第2A型接受體T102C 基因多型性、血清素運送基因多型性與血清素第2C型接受體Cys23Ser基因多型性與慢性精神分裂症患者之TD有無相關。 方法：本研究屬於遺傳的相關性研究。評估於台灣具代表性的兩家精神科專科醫院之慢性住院精神分裂症病患，再以有無TD現象分為TD組 (n=32)與non-TD組 (n=135)，並有正常對照組 (n=91)參與，所有參加者皆為台灣漢族人。實驗室方面將抽血得到之白血球所抽出的DNA進行聚合鏈反應，以瞭解各基因多型性在TD組與non-TD組的分布是否有差異。並以logistic regression 調整相關變項，及根據年齡與性別做次族群的分析。 結果：於血清素第2A型接受體基因，TD組相較於non-TD組有較少的CC及CT基因型 (P=0.022)；C allele frequency於TD組為29.7%，於non-TD組為45.6%，兩組的allele分布亦已達統計上顯著差異 (P=0.021)。經logistic regression調整變項後，TD的有無僅與血清素第2A型接受體基因多型性有統計上的相關，特別是在顯性模式 (OR=0.26, 95%CI=0.10-0.71, P=0.008) 與加成性模式 (OR=0.40, 95% CI=0.19-0.86, P=0.019)。於血清素運送基因多型性與血清素第2C型接受體基因多型性則與TD沒有相關。於次族群分析，年齡大於等於50 歲 (OR=0.28, 95% CI=0.10-0.84, P=0.022) 及男性病患 (OR=0.033, 95% CI=0.003-0.37, P=0.006)，其血清素2A接受體基因多型性與TD相關。 結論：本研究發現血清素第2A型接受體T102C基因多型性，會影響台灣漢族慢性精神分裂症患者的TD發生。

Background and Objective: Tardive dyskinesia (TD) is a serious side effect of antipsychotics. Although the pathogenesis of TD is still not fully understood, studies have reported TD is associated with serotonin genes. This study is aimed at exploring the association between the serotonin gene polymorphisms (HTR2A T102C, 5-HTTLPR, HTR2C Cys23Ser) and chronic schizophrenic patients with or without TD. Methods: Genetic association study with case control design was performed to analyze the allele and genotype frequencies of schizophrenia patients with TD (n=32), patients without TD (n=135), and normal control participants (n=91). All participants are Ethnic Han Taiwanese. Genotyping of HTR2A T102C polymorphism, 5-HTTLPR polymorphism and HTR2C Cys23Ser polymorphism were performed by polymerase chain reaction-based restriction analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by multivariate logistic regression analysis. Subgroup analysis was performed according to age and gender. Results: The C allele frequency of HTR2A is 29.7% in TD group and 45.6% in non-TD group (P=0.021). Patients carrying C allele were likely to be protected from TD (OR=0.26, 95% CI=0.10-0.71, P=0.008 for dominant mode; OR=0.40, 95% CI=0.19-0.86, P=0.019 for additive mode). However, no association between 5-HTTLPR and HTR2C polymorphisms and TD was found. HTR2A T102C was associated with TD in subgroup of older than 50 years (OR=0.28, 95% CI=0.10-0.84, P=0.022) and men (OR=0.033, 95% CI=0.003-0.37, P=0.006). Conclusion: Our findings support that HTR2A T102C polymorphism influences the susceptibility to antipsychotics-induced TD in the chronic schizophrenic patients in Taiwan.