Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
Human Genetics, University of Navarra, Navarra, Spain.
PLoS One. 2018 May 23;13(5):e0197975. doi: 10.1371/journal.pone.0197975. eCollection 2018.
Huntington's disease (HD) age of onset (AO) is mainly determined by the length of the CAG repeat expansion in the huntingtin gene. The remaining AO variability has been attributed to other little-known factors. A factor that has been associated with other neurodegenerative diseases is arterial hypertension (AHT). The aim of this study is to evaluate the contribution of AHT to the AO of HD. We used data from a cohort of 630 European HD patients with adult onset collected by the REGISTRY project of the European Huntington's Disease Network. Multiple linear regression and ANOVA, controlling for the CAG repeat number of the expanded allele (CAGexp) of each patient, were performed to assess the association between the AHT condition and the AO of the motor symptoms (mAO). The results showed a significant association between AHT and mAO, especially when we only considered the patients diagnosed with AHT prior to manifesting any HD signs (pre-HD AHT). Remarkably, despite the low number of cases, those patients developed motor symptoms 5-8 years later than normotensive patients in the most frequent CAGexp range (40-44). AHT is an age-related condition and consequently, the age of the patient at the time of data collection could be a confounder variable. However, given that most pre-HD AHT patients included in our study had started treatment with antihypertensive drugs prior to the onset of HD, and that antihypertensive drugs have been suggested to confer a neuroprotective effect in other neurodegenerative diseases, raises the interest in elucidating the impact of AHT and/or AHT treatment in HD age of onset in further studies. A confirmation of our results in a larger sample set would open the possibility to significantly improve HD management.
亨廷顿病(HD)的发病年龄(AO)主要由亨廷顿基因中 CAG 重复扩展的长度决定。其余的 AO 可变性归因于其他鲜为人知的因素。与其他神经退行性疾病相关的一个因素是动脉高血压(AHT)。本研究旨在评估 AHT 对 HD 的 AO 的贡献。我们使用了欧洲亨廷顿病网络 REGISTRY 项目收集的 630 名患有成年发病 HD 的欧洲患者的数据。为了评估 AHT 状况与运动症状(mAO)的 AO 之间的关联,我们对每位患者的扩张等位基因(CAGexp)的 CAG 重复数进行了多元线性回归和方差分析。结果显示,AHT 与 mAO 之间存在显著关联,尤其是当我们仅考虑在出现任何 HD 迹象之前被诊断为 AHT 的患者时(pre-HD AHT)。值得注意的是,尽管病例数较少,但在最常见的 CAGexp 范围内(40-44),与血压正常的患者相比,这些患者出现运动症状的时间晚了 5-8 年。AHT 是一种与年龄相关的疾病,因此,患者在数据收集时的年龄可能是一个混杂变量。然而,鉴于我们研究中纳入的大多数 pre-HD AHT 患者在 HD 发病前已经开始接受降压药物治疗,并且降压药物在其他神经退行性疾病中被认为具有神经保护作用,这引起了人们对阐明 AHT 和/或 AHT 治疗对 HD 发病年龄的影响的兴趣。在更大的样本集中确认我们的结果将有可能显著改善 HD 的管理。