GBA variants in REM sleep behavior disorder: A multicenter study.
GBA variants in REM sleep behavior disorder: A multicenter study.
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DOI：
10.1212/wnl.0000000000010042
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发表时间：
2020-08-25
期刊：
影响因子：
9.9
通讯作者：
Gan-Or Z
中科院分区：
文献类型：
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作者：
Krohn L;Ruskey JA;Rudakou U;Leveille E;Asayesh F;Hu MTM;Arnulf I;Dauvilliers Y;Högl B;Stefani A;Monaca CC;Abril B;Plazzi G;Antelmi E;Ferini-Strambi L;Heidbreder A;Boeve BF;Espay AJ;De Cock VC;Mollenhauer B;Sixel-Döring F;Trenkwalder C;Sonka K;Kemlink D;Figorilli M;Puligheddu M;Dijkstra F;Viaene M;Oertel W;Toffoli M;Gigli GL;Valente M;Gagnon JF;Desautels A;Montplaisir JY;Postuma RB;Rouleau GA;Gan-Or Z
研究GBA变异在孤立性快速眼动睡眠行为障碍（iRBD）和转化为显性神经变性风险中的作用。共纳入4147人：1061例iRBD患者和3086例对照。利用分子倒置探针和Sanger测序对GBA进行全测序。我们分析了GBA变异对iRBD风险、发病年龄（AAO）和转换率的影响。9.5%的iRBD患者发现GBA变异，而对照组为4.1%（优势比为2.45；95%可信区间[CI]， 1.87-3.22; p = 1 × 10−10）。轻度p. n370s变异携带者的OR值为3.69 (95% CI, 1.90-7.14; p = 3.5 × 10−5)，而重度变异携带者的OR值为17.55 （95% CI, 2.11-145.9; p = 0.0015）。严重GBA变异携带者的平均AAO为52.8年，比轻度变异或非携带者早7-8年（p = 0.029）。在有可用数据的GBA变异携带者中，52.5%的人已经转化，而非携带者的比例为35.6% (p = 0.011)，严重GBA变异携带者的转化速度更快。然而，关于AAO和转化率的结果是基于小数字的，应该谨慎解释。GBA变异体显著且有差异地增加iRBD的风险。在严重的GBA变异携带者中，转化为神经变性的比率也会增加，并且可能更快，尽管需要在更大的样本中进行确认。在健康的GBA变异体携带者中筛查RBD，作为识别将来可能发生突触核蛋白病的GBA变异体携带者的潜在方法。
To study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration. A total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates. GBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87–3.22; p = 1 × 10−10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90–7.14; p = 3.5 × 10−5), while for severe variant carriers it was 17.55 (95% CI, 2.11–145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7–8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution. GBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.