Head injury, α-synuclein Rep1, and Parkinson's disease.
Head injury, α-synuclein Rep1, and Parkinson's disease.
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DOI：
10.1002/ana.22499
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发表时间：
2012-01
影响因子：
11.2
通讯作者：
Tanner, Caroline M.
中科院分区：
文献类型：
--
作者：
Goldman, Samuel M.;Kamel, Freya;Ross, G. Webster;Jewell, Sarah A.;Bhudhikanok, Grace S.;Umbach, David;Marras, Connie;Hauser, Robert A.;Jankovic, Joseph;Factor, Stewart A.;Bressman, Susan;Lyons, Kelly E.;Meng, Cheryl;Korell, Monica;Roucoux, Diana F.;Hoppin, Jane A.;Sandler, Dale P.;Langston, J. William;Tanner, Caroline M.
为了验证SNCA Rep1（编码α-突触核蛋白的基因启动子区域的多态二核苷酸微卫星）的变异是否改变了头部损伤与帕金森病（PD）风险之间的关系。农业和运动评估（FAME）和环境关联与帕金森病风险研究使用病例对照历史访谈（SEARCH），两项独立病例对照研究的参与者进行了Rep1基因分型，并对PD诊断前头部损伤伴有意识丧失或脑震荡的参与者进行了访谈。Logistic回归模型校正了潜在的混杂变量，并检验了Rep1基因型与头部损伤之间的相互作用。与先前的报道一致，相对于中等长度的Rep1，短Rep1基因型与PD风险降低相关（合并优势比（OR） 0.7, 95%可信区间（CI） 0.5-0.9），而长Rep1基因型与PD风险增加相关（合并优势比（OR） 1.4, 95%可信区间（CI） 0.95-2.2）。总体而言，头部损伤与PD无显著相关性（合并OR为1.3,95%CI为0.9-1.8）。然而，在Rep1较长的患者中，头部损伤与PD密切相关（FAME OR 5.4, 95%CI 1.5-19; SEARCH OR 2.3, 95%CI 0.6-9.2; pooled OR 3.5, 95%CI 1.4-9.2， p交互作用0.02）。有头部损伤和长Rep1的个体比没有危险因素的个体早诊断4.9年（p = 0.03）。虽然头部损伤本身与PD风险无关，但我们的数据表明，当突触核蛋白水平较高时，例如Rep1扩增的患者，头部损伤可能会启动和/或加速神经退行性变。鉴于头部损伤的高人群频率，这些结果的独立验证是必不可少的。
To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson’s disease (PD) risk. Participants in Farming and Movement Evaluation (FAME) and Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), two independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to PD diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury. Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio (OR) 0.7, 95% confidence interval (CI) 0.5-0.9), and long Rep1 with increased risk (pooled OR 1.4, 95%CI 0.95-2.2). Overall, head injury was not significantly associated with PD (pooled OR 1.3, 95%CI 0.9-1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR 5.4, 95%CI 1.5-19; SEARCH OR 2.3, 95%CI 0.6-9.2; pooled OR 3.5, 95%CI 1.4-9.2, p-interaction 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03). While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential.
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