GBA1突变和APOE基因多态性对阿什肯纳兹犹太路易体痴呆患者生存及病情进展的影响
Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies.
作者信息
Shiner Tamara, Kavé Gitit, Mirelman Anat, Regev Keren, Piura Yoav, Goldstein Orly, Gana Weisz Mali, Bar-Shira Anat, Gurevich Tanya, Orr-Urtreger Avi, Alcalay Roy N, Giladi Nir, Bregman Noa
机构信息
Cognitive Neurology Unit, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
出版信息
Mov Disord. 2024 Dec;39(12):2280-2285. doi: 10.1002/mds.30003. Epub 2024 Aug 30.
BACKGROUND
Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.
OBJECTIVE
To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.
METHODS
One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.
RESULTS
GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.
CONCLUSION
Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.
背景
葡糖脑苷脂酶1（GBA1）突变与帕金森病患者生存率降低有关，但其对路易体痴呆（DLB）患者生存率的影响尚不清楚。
目的
在控制载脂蛋白E（APOE）状态的同时，评估GBA1突变对阿什肯纳兹犹太裔DLB患者生存率的影响。
方法
对来自以色列特拉维夫医疗中心的140名参与者进行GBA1突变和APOE多态性基因分型。分析生存率和随访认知筛查分数。
结果
GBA1突变携带者的死亡风险增加两倍（风险比=1.999），而APOE状态并不独立影响生存率。在有可用临床数据的患者亚组（n=63）中，APOEε4等位基因携带者的认知功能衰退更快，而GBA1突变携带者的衰退速度也更快，尽管差异不显著。
结论
了解基因对生存和疾病进展的影响对于患者咨询和纳入临床试验至关重要。
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