Department of Neurology, Graduate School of Medicine, University of Tokyo Tokyo, Japan.
Department of Neurology, Hokkaido University Graduate School of Medicine Sapporo, Japan.
Ann Clin Transl Neurol. 2015 Apr;2(4):417-26. doi: 10.1002/acn3.185. Epub 2015 Feb 28.
Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series.
We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants.
In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10(-3)).
The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
导致戈谢病的葡萄糖脑苷脂酶基因（GBA）变异与帕金森病（PD）和路易体痴呆（DLB）有关。为了研究 GBA 变异在多系统萎缩（MSA）中的作用，我们在一个大型病例对照系列中分析了 GBA 变异。
我们对 969 例 MSA 患者（574 例日本、223 例欧洲和 172 例北美）和 1509 例对照者（900 例日本、315 例欧洲和 294 例北美）的 GBA 编码区和侧翼剪接位点进行了测序。我们只关注导致戈谢病的 GBA 变异。
在日本系列中，我们在 MSA 患者中发现了 9 名携带者（1.65%）和 8 名携带者在对照组中（0.89%）。在欧洲系列中，我们在 MSA 患者中发现了 3 名携带者（1.35%）和 2 名携带者在对照组中（0.63%）。在北美系列中，我们在 MSA 患者中发现了 5 名携带者（2.91%）和 1 名携带者在对照组中（0.34%）。对每个系列进行 Mantel-Haenszel 分析得出的合并优势比（OR）为 2.44（95%置信区间[CI]，1.14-5.21），P 值为 0.029，无明显异质性证据。逻辑回归分析得到了类似的结果，调整后的 OR 为 2.43（95%CI 1.15-5.37），P 值为 0.022。亚组分析表明，导致戈谢病的 GBA 变异与 MSA 小脑亚型（MSA-C）患者显著相关（P=7.3×10(-3)）。
这些发现表明，与 PD 和 DLB 一样，导致戈谢病的 GBA 变异与 MSA 相关。
