Al Hadithy A F Y, Ivanova S A, Pechlivanoglou P, Wilffert B, Semke A, Fedorenko O, Kornetova E, Ryadovaya L, Brouwers J R B J, Loonen A J M
Erasmus University Medical Center, Hospital Pharmacy, Rotterdam, the Netherlands.
Hum Psychopharmacol. 2010 Jan;25(1):84-91. doi: 10.1002/hup.1087.
Neuronal degeneration due to oxidative stress (OS) has been proposed as a mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms against OS may involve detoxification enzymes (e.g., glutathione peroxidase-1, GPX1; superoxide dismutase-2, SOD2 [also commonly known as MnSOD]; and glutathione S-transferase P1, GSTP1). Several pharmacogenetic studies have examined TD and OS in different ethnic groups, but not in Russians. Here we report the association between orofaciolingual (TDof) and limb-truncal dyskinesias (TDlt) and polymorphisms of GSTP1 (Ile105Val), MnSOD (Ala-9Val), and GPX1 (Pro197Leu) genes in 146 Russian inpatients from Siberia. We applied AIMS instrument to rate dyskinesias. Two-part model analyses, logistic and multivariate parametric regressions were applied to assess the effects of different variables (e.g., genotype, age, gender, and medication use). Our analyses do not suggest that Pro197Leu (GPX1) is associated with TD. However, our analyses suggest that the 105Val-allele of Ile105Val (GSTP1) may be associated with a lower risk and a severity of TDof and TDlt and that Ile105Val pharmacogenetics may be different in Slavonic Caucasians from that in American Caucasians. Furthermore, we find evidence for an association between Ala-9Val (MnSOD) and TDof, but not TDlt. Subject to further replication, our findings extend the available knowledge on the pharmacogenetics of TD and oxidative stress.
氧化应激（OS）导致的神经元变性被认为是迟发性运动障碍（TD）发病机制之一。细胞对抗OS的防御机制可能涉及解毒酶（如谷胱甘肽过氧化物酶-1，GPX1；超氧化物歧化酶-2，SOD2[也通常称为锰超氧化物歧化酶，MnSOD]；以及谷胱甘肽S-转移酶P1，GSTP1）。多项药物遗传学研究已在不同种族群体中研究了TD与OS，但未涉及俄罗斯人。在此，我们报告了146名来自西伯利亚的俄罗斯住院患者的口面部（TDof）和肢体-躯干运动障碍（TDlt）与GSTP1（Ile105Val）、锰超氧化物歧化酶（Ala-9Val）和GPX1（Pro197Leu）基因多态性之间的关联。我们应用异常不自主运动量表（AIMS）评估运动障碍。采用两部分模型分析、逻辑回归和多变量参数回归来评估不同变量（如基因型、年龄、性别和药物使用）的影响。我们的分析未表明Pro197Leu（GPX1）与TD相关。然而，我们的分析表明，Ile105Val（GSTP1）的105Val等位基因可能与TDof和TDlt的较低风险及严重程度相关，并且Ile105Val药物遗传学在斯拉夫白种人与美国白种人中可能存在差异。此外，我们发现Ala-9Val（锰超氧化物歧化酶）与TDof相关，但与TDlt无关的证据。有待进一步验证，我们的研究结果扩展了关于TD药物遗传学和氧化应激的现有知识。
