New York University School of Medicine, New York, NY 10016, USA.
Parkinsonism Relat Disord. 2013 Jan;19(1):129-31. doi: 10.1016/j.parkreldis.2012.06.023. Epub 2012 Aug 31.
Gaucher disease is an autosomal recessive disorder caused by glucocerebrosidase gene mutations. Accumulating evidence from several Parkinson's disease cohorts of varying ethnicities suggests that glucocerebrosidase mutations even in the heterozygous state (carriers) may be a susceptibility factor for Parkinson's. Very few studies have analyzed the frequency of Parkinson's in carriers and individuals with Gaucher disease.
To determine frequency of Parkinson's in patients with Gaucher disease and obligate carriers of glucocerebrosidase mutations and compare it with a control group.
A questionnaire was completed by 100 Ashkenazi Jewish Gaucher patients followed at our center and 109 ethnicity-matched controls with no personal or family history of Gaucher disease.
Frequency of Parkinson's was higher in Gaucher patients (8/100) than in controls (0/109; P = 0.0024). Frequency of Parkinson's in obligate carriers (11/200) was higher than controls (6/218), but the difference was not statistically significant (P = 0.215). Average age of onset of Parkinson's was earlier in Gaucher patients (57.2) than the general population and in obligate carriers (60) when compared with controls (76.8; P = 0.01). The L444P genotype was more frequent in Gaucher patients who reported a parent with Parkinson's (36.40%) than those who did not (4.50%).
Our study suggests that the risk for developing Parkinson's may be higher in affected versus carriers of glucocerebrosidase mutations and suggests that L444P may pose a higher risk of developing Parkinson's than other mutations. It also confirms previous findings that the age of onset of Parkinson's associated with glucocerebrosidase mutations is earlier than in the general population.
戈谢病是一种常染色体隐性遗传疾病，由葡萄糖脑苷脂酶基因突变引起。来自不同种族的多个帕金森病队列的越来越多的证据表明，葡萄糖脑苷脂酶突变即使在杂合状态（携带者）下也可能是帕金森病的易感因素。很少有研究分析过戈谢病患者和葡萄糖脑苷脂酶突变的强制性携带者中帕金森病的频率。
确定戈谢病患者和葡萄糖脑苷脂酶突变的强制性携带者中帕金森病的频率，并与对照组进行比较。
我们中心随访的 100 名阿什肯纳兹犹太裔戈谢病患者和 109 名无戈谢病个人或家族史的种族匹配对照者完成了一份问卷。
戈谢病患者中帕金森病的发生率（8/100）高于对照组（0/109；P = 0.0024）。强制性携带者（11/200）中帕金森病的发生率高于对照组（6/218），但差异无统计学意义（P = 0.215）。与对照组相比，帕金森病在戈谢病患者（57.2 岁）和强制性携带者（60 岁）中的发病年龄更早（P = 0.01）。在报告父母患有帕金森病的戈谢病患者中，L444P 基因型更为常见（36.40%），而在没有报告父母患有帕金森病的患者中则更为少见（4.50%）。
我们的研究表明，葡萄糖脑苷脂酶突变的受影响者比携带者发生帕金森病的风险更高，并且表明 L444P 可能比其他突变具有更高的发展为帕金森病的风险。它还证实了先前的发现，即与葡萄糖脑苷脂酶突变相关的帕金森病发病年龄早于普通人群。
