Dulski Jarosław, Uitti Ryan J, Ross Owen A, Wszolek Zbigniew K
Department of Neurology, Mayo Clinic, Jacksonville, FL, United States.
Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdańsk, Gdańsk, Poland.
Front Aging Neurosci. 2022 Oct 20;14:1023574. doi: 10.3389/fnagi.2022.1023574. eCollection 2022.
The heterogeneity of Parkinson's disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies.
帕金森病（PD）的异质性自200多年前詹姆斯·帕金森对其进行描述以来就已被认识到。帕金森病运动和非运动表现的复杂性促使人们多次尝试对帕金森病进行亚型分类，并得出不同的预后结果；然而，帕金森病异质性的病理生理基础仍然难以捉摸。帕金森病的遗传因素可能有助于理解帕金森病亚型的基础。因此，识别基因型-表型关联对于成功的基因治疗可能至关重要。我们回顾了帕金森病亚型潜在遗传结构的知识现状，讨论了单基因形式以及与各种帕金森病亚型相关的寡基因和多基因风险因素。基于我们的综述，我们主张统一帕金森病亚型分类，区分帕金森病遗传因素和遗传修饰因子的研究，并重复先前研究的结果。
