Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan.
Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):229-34. doi: 10.1002/ajmg.b.30977.
Early onset Parkinson's disease (PD) has been associated with mutations in Parkin. We screened Parkin mutations in a cohort of Taiwanese early onset PD using direct cDNA sequencing. Two deletions (Ex2-3del and Ex5del), one point mutation (R334C), one 86-bp IVS9 insertion (c.1084intron(+)), and two polymorphisms (S167N and V380L) were identified. The mutations identified are heterozygous and none of the mutation carriers possess two Parkin mutations. The c.1084intron(+) was due to a novel IVS9 g > a change. To assess the association of IVS9 g > a, S167N and V380L with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. Although the difference is not significant, the V380L C allele frequency was notably lower in PD patients than the controls and a trend toward decrease in risk of developing PD was evident (odds ratio: 0.71, 95% confidence interval: 0.53-0.97, P = 0.029). Contrarily the IVS9 g > a a allele frequency was notably higher in PD patients than the controls and a trend toward increase in risk of developing PD was also evident (odds ratio: 1.65, 95% confidence interval: 1.06-2.59, P = 0.028). Quantitative real-time PCR showed that the relative Parkin c.1084intron(+) mRNA expression was increased in PD patients with IVS9 ga genotype as compared to gg genotype. Pairwise genotype analysis revealed that IVS9 gg genotype strengthens the negative association of the V380L GC genotype with PD (odds ratio: 0.67, 95% confidence interval: 0.48-0.94, P = 0.021). The results of Parkin mutation/polymorphism screening may contribute to our understanding of PD.
早发性帕金森病（PD）与 Parkin 基因突变有关。我们使用直接 cDNA 测序筛选了台湾早发性 PD 患者的 Parkin 突变。发现了两种缺失（Ex2-3del 和 Ex5del）、一种点突变（R334C）、一种 86bp IVS9 插入（c.1084intron(+))，以及两种多态性（S167N 和 V380L）。所鉴定的突变是杂合子，并且没有突变携带者具有两种 Parkin 突变。c.1084intron(+) 是由于新的 IVS9 g > a 变化引起的。为了评估 IVS9 g > a、S167N 和 V380L 与 PD 风险的关联，我们在 PD 患者和与之匹配的对照组中进行了病例对照研究。尽管差异不显著，但 PD 患者的 V380L C 等位基因频率明显低于对照组，并且 PD 发病风险呈下降趋势（比值比：0.71，95%置信区间：0.53-0.97，P = 0.029）。相反，IVS9 g > a 等位基因频率在 PD 患者中明显高于对照组，PD 发病风险也呈上升趋势（比值比：1.65，95%置信区间：1.06-2.59，P = 0.028）。实时定量 PCR 显示，与 IVS9 gg 基因型相比，IVS9 ga 基因型 PD 患者的 Parkin c.1084intron(+) mRNA 表达增加。成对基因型分析显示，IVS9 gg 基因型增强了 V380L GC 基因型与 PD 的负相关（比值比：0.67，95%置信区间：0.48-0.94，P = 0.021）。Parkin 突变/多态性筛选的结果可能有助于我们理解 PD。
