PDF(Pubmed)
Abstract：
Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson\'s disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD.
Seventy-four subjects, including 38 patients with PD and 36 age-matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron-related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted.
Four strong SNP-QT associations were detected: rs602201-susceptibility of bilateral SN, rs198440-susceptibility of left SN, and rs7895403-susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A- genotype of rs602201 and G allele/G- genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A- genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G- carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP-by-disease interaction in bilateral SN.
This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron-related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic-based.
Seventy-four subjects, including 38 patients with PD and 36 age-matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron-related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted.
Four strong SNP-QT associations were detected: rs602201-susceptibility of bilateral SN, rs198440-susceptibility of left SN, and rs7895403-susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A- genotype of rs602201 and G allele/G- genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A- genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G- carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP-by-disease interaction in bilateral SN.
This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron-related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic-based.
摘要：
背景：铁代谢障碍，特别是在黑质(SN)中，在帕金森病（PD）中得到广泛认可，但是遗传对铁沉积的影响在很大程度上仍然未知。因此，在这项研究中，我们的目的是研究遗传对PD中铁沉积的潜在影响。
方法：74个科目，包括38例PD患者和36例年龄匹配的正常对照,参与了这项研究。成像遗传关联分析用于鉴定单核苷酸多态性（SNP）对铁相关数量性状（QT）的特定影响。在疾病水平上对铁沉积的遗传影响，SNP水平，并突出了它们的互动效果。
结果：检测到四种强SNP-QT关联：rs602201-双侧SN的易感性，rs198440-左侧SN的磁化率,和rs7895403-左尾状头的敏感性。详细的分析表明：（1）在PD的双侧SN中发现了显着的铁沉积；（2）在PD中更频繁地观察到rs602201的A等位基因/A基因型和rs198440和rs7895403的G等位基因/G基因型的多态性改变；（3）对于rs602201，在所有受试者中，双侧SN中A-基因型携带者的铁含量明显高于TT基因型。对于rs198440和rs7895403，G-携带者在左侧SN和左侧尾状头中的铁含量高于AA基因型。分别；（4）rs602201在双侧SN中表现出明显的SNP-疾病相互作用。
结论：这项研究表明，rs602201和rs198440对PD中的黑色铁沉积有促进作用，这提供了对PD中铁相关发病机制的更好理解，特别是,SN中铁沉积的脆弱性是基于遗传的。
方法：74个科目，
结果：检测到四种强SNP-QT关联：rs602201-双侧SN的易感性，
结论：这项研究表明，rs602201和rs198440对PD中的黑色铁沉积有促进作用，
