Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland; Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Laboratory for Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Parkinsonism Relat Disord. 2017 Dec;45:39-43. doi: 10.1016/j.parkreldis.2017.09.021. Epub 2017 Sep 29.
Variation contributing to the risk of Parkinson's disease (PD) has been identified in several genes and at several loci including GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT, but the frequencies of risk variants seem to vary according to ethnic background. Our aim was to analyze how variation in these genes contributes to PD in the Finnish population.
The subjects consisted of 527 Finnish patients with early-onset PD, 325 patients with late-onset PD and 403 population controls. We screened for known genetic risk variants in GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT. In addition, DNA from 225 patients with early-onset Parkinson's disease was subjected to whole exome sequencing (WES).
We detected a significant difference in the length variation of the CAG repeat in POLG1 between patients with early-onset PD compared to controls. The p.N370S and p.L444P variants in GBA contributed to a relative risk of 3.8 in early-onset PD and 2.5 in late-onset PD. WES revealed five variants in LRRK2 and SMPD1 that were found in the patients but not in the Finnish ExAC sequences. These are possible risk variants that require further confirmation. The p.G2019S variant in LRRK2, common in North African Arabs and Ashkenazi Jews, was not detected in any of the 849 PD patients.
The POLG1 CAG repeat length variation and the GBA p.L444P variant are associated with PD in the Finnish population.
帕金森病（PD）风险的变异已在多个基因和多个基因座中被鉴定，包括 GBA、SMPD1、LRRK2、POLG1、CHCHD10 和 MAPT，但风险变异的频率似乎因种族背景而异。我们的目的是分析这些基因中的变异如何导致芬兰人群中的 PD。
研究对象包括 527 名芬兰早发性 PD 患者、325 名晚发性 PD 患者和 403 名人群对照。我们筛查了 GBA、SMPD1、LRRK2、POLG1、CHCHD10 和 MAPT 中的已知遗传风险变异。此外，对 225 名早发性帕金森病患者的 DNA 进行了全外显子组测序（WES）。
我们检测到 POLG1 中 CAG 重复序列长度变异在早发性 PD 患者与对照组之间存在显著差异。GBA 中的 p.N370S 和 p.L444P 变异导致早发性 PD 的相对风险为 3.8，晚发性 PD 的相对风险为 2.5。WES 揭示了 LRRK2 和 SMPD1 中的五个变体，这些变体仅在患者中发现，而不在芬兰 ExAC 序列中发现。这些可能是需要进一步确认的风险变体。在 849 名 PD 患者中未检测到常见于北非阿拉伯人和阿什肯纳兹犹太人的 LRRK2 p.G2019S 变体。
POLG1 CAG 重复长度变异和 GBA p.L444P 变体与芬兰人群中的 PD 相关。
