ALS phenotype is influenced by age, sex, and genetics: A population-based study
ALS phenotype is influenced by age, sex, and genetics: A population-based study
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DOI：
10.1212/wnl.0000000000008869
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发表时间：
2020-02-25
期刊：
影响因子：
9.9
通讯作者：
Calvo, Andrea
中科院分区：
文献类型：
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作者：
Chio, Adriano;Moglia, Cristina;Calvo, Andrea
目的评估肌萎缩侧索硬化症（ALS）表型的决定因素在一个基于人群的coholty.MethodsThe研究人群包括2，839例确诊为ALS患者在皮埃蒙特，意大利（1995-2015）。根据运动（典型、延髓、连枷臂、连枷腿、主要是上运动神经元[ALBN]、呼吸）和认知表型（正常、ALS伴认知损害[ALSci]、ALS伴行为损害[ALSbi]、ALSci和ALSbi联合[ALScbi]、ALS-额颞叶痴呆[FTD]）对患者进行分类。二元logistic回归分析调整了性别、年龄和遗传因素。（p < 0.0001），随着年龄的增长，女性比男性受影响更大（p < 0.0001），年龄较小的经典型（p = 0.029），随着年龄的增长，男性比女性受到的影响更大（p < 0.0001），年龄越小，（p < 0.0001），男性连枷臂（p < 0.0001）和年轻年龄（p = 0.04），连枷腿随年龄增长男性（p = 0.008），呼吸道疾病随年龄增长男性（p < 0.0001）。C9 orf 72扩增与延髓表型相关（p < 0.0001），在延髓中较不常见（p = 0.041）; SOD 1突变与连枷腿表型相关（p < 0.0001），在延髓中较不常见（p < 0.0001）。ALS-FTD与C9 orf 72相关（p < 0.0001）和延髓表型（p = 0.008），ALScbi + ALBN（p = 0.014），和老年人的ALSci（p = 0.008）。结论我们的数据表明，空间-导致ALS发作和进展的运动和认知事件的时间组合的特征在于对ALS的病理过程的不同易感性。运动和前额叶皮质和下运动神经元，并受年龄，性别和基因变异的影响。这些调节ALS表型的因素的鉴定将使我们能够将患者重新分类为病理同质的亚组，对靶向个性化治疗有反应。
ObjectiveTo assess the determinants of amyotrophic lateral sclerosis (ALS) phenotypes in a population-based cohort.MethodsThe study population included 2,839 patients with ALS diagnosed in Piemonte, Italy (1995-2015). Patients were classified according to motor (classic, bulbar, flail arm, flail leg, predominantly upper motor neuron [PUMN], respiratory) and cognitive phenotypes (normal, ALS with cognitive impairment [ALSci], ALS with behavioral impairment [ALSbi], ALSci and ALSbi combined [ALScbi], ALS-frontotemporal dementia [FTD]). Binary logistic regression analysis was adjusted for sex, age, and genetics.ResultsBulbar phenotype correlated with older age (p < 0.0001), women were more affected than men at increasing age (p < 0.0001), classic with younger age (p = 0.029), men were more affected than women at increasing age (p < 0.0001), PUMN with younger age (p < 0.0001), flail arm with male sex (p < 0.0001) and younger age (p = 0.04), flail leg with male sex with increasing age (p = 0.008), and respiratory with male sex (p < 0.0001). C9orf72 expansions correlated with bulbar phenotype (p < 0.0001), and were less frequent in PUMN (p = 0.041); SOD1 mutations correlated with flail leg phenotype (p < 0.0001), and were less frequent in bulbar (p < 0.0001). ALS-FTD correlated with C9orf72 (p < 0.0001) and bulbar phenotype (p = 0.008), ALScbi with PUMN (p = 0.014), and ALSci with older age (p = 0.008).ConclusionsOur data suggest that the spatial-temporal combination of motor and cognitive events leading to the onset and progression of ALS is characterized by a differential susceptibility to the pathologic process of motor and prefrontal cortices and lower motor neurons, and is influenced by age, sex, and gene variants. The identification of those factors that regulate ALS phenotype will allow us to reclassify patients into pathologically homogenous subgroups, responsive to targeted personalized therapies.