Pulkes Teeratorn, Choubtum Lulin, Chitphuk Sermsiri, Thakkinstian Ammarin, Pongpakdee Sunsanee, Kulkantrakorn Kongkiat, Hanchaiphiboolkul Suchat, Tiamkao Somsak, Boonkongchuen Pairoj
Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Parkinsonism Relat Disord. 2014 Sep;20(9):986-91. doi: 10.1016/j.parkreldis.2014.06.007. Epub 2014 Jun 23.
GBA mutations are an important risk factor in developing Parkinson's disease (PD) worldwide. The study aimed to determine the frequency and clinical characteristics of GBA mutations in a Thai PD cohort of 480 patients and 395 control subjects.
Direct sequencing of GBA was performed in all early-onset PD patients (EOPD: n = 108) and 100 PD patients with age at onset over 50 years (AAO > 50y-PD). The study subsequently screened all identified mutations in the remaining AAO > 50y-PD patients and all control subjects. Predictive factors associated with risk of developing PD were analyzed. Comparisons of clinical characteristics of PD patients with and without GBA mutations were also carried out.
Heterozygous GBA mutations were identified in 24 patients (5%) and 2 controls (0.5%). Seven identified GBA point mutations comprised p.L444P, p.N386K, p.P428S, IVS2+1G > A, IVS9+3G > C, IVS10-9_10GT > AG and c.1309delG, of which five mutations were novel. Multiple logistic regression analysis revealed that GBA mutations were more frequent in EOPD than AAO > 50y-PD groups (OR = 4.64, P < 0.022). Patients with GBA mutations had mean age at onset (43.1 ± 10.2, mean ± standard deviation) earlier than patients without GBA mutations (54.4 ± 13.9, P = 0.002). The patients with GBA mutations also had a more rapid progressive course, in which they were more likely to have higher Hoehn and Yahr staging (OR = 4.20, P = 0.006) and slightly lower means of Schwab-England ADL score [74.1 ± 17.1 vs. 81.0 ± 18.08 (OR = 0.98, 95%CI = 0.96-1.01, P = 0.162)].
GBA mutations are an important risk of PD in the Thai population. Patients having the mutations are likely to have early onset and may exhibit more rapid motor progression.
在全球范围内，GBA基因突变是帕金森病（PD）发病的一个重要风险因素。本研究旨在确定480例泰国PD患者队列和395例对照受试者中GBA基因突变的频率及临床特征。
对所有早发型PD患者（EOPD：n = 108）和100例发病年龄超过50岁的PD患者（AAO>50y - PD）进行GBA基因直接测序。随后，对其余AAO>50y - PD患者和所有对照受试者筛查所有已鉴定的突变。分析与PD发病风险相关的预测因素。还对有和无GBA基因突变的PD患者的临床特征进行了比较。
在24例患者（5%）和2例对照（0.5%）中鉴定出杂合GBA基因突变。鉴定出的7个GBA点突变包括p.L444P、p.N386K、p.P428S、IVS2 + 1G>A、IVS9 + 3G>C、IVS10 - 9_10GT>AG和c.1309delG，其中5个突变是新发现的。多因素logistic回归分析显示，EOPD组中GBA基因突变比AAO>50y - PD组更常见（OR = 4.64，P < 0.022）。有GBA基因突变的患者发病平均年龄（43.1±10.2，均值±标准差）早于无GBA基因突变的患者（54.4±13.9，P = 0.002）。有GBA基因突变的患者病程进展也更快，他们更有可能具有更高的Hoehn和Yahr分期（OR = 4.20，P = 0.006），且Schwab - England日常生活活动能力评分均值略低[74.1±17.1 vs. 81.0±18.08（OR = 0.98，95%CI = 0.96 - 1.01，P = 0.162）]。
GBA基因突变是泰国人群中PD的一个重要风险因素。有这些突变的患者可能发病较早，且可能表现出更快的运动进展。
