Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis.
Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis.
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DOI：
10.1136/jnnp-2021-327133
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Turner MR
中科院分区：
文献类型：
--
作者：
Thompson AG;Talbot K;Turner MR
发病前体重指数、身体活动、糖尿病和心血管疾病与发生肌萎缩侧索硬化症（ALS）的风险改变有关。有证据表明ALS和脂质代谢有共同的遗传风险。一个非常大的前瞻性纵向人群队列允许研究一系列代谢参数和随后诊断ALS的风险。前瞻性纳入UK Biobank的患者（n=502 409）的后续ALS诊断风险与血液高、低密度脂蛋白（HDL、LDL）、总胆固醇、总胆固醇：HDL比值、载脂蛋白A1和B （apoA1、apoB）、甘油三酯、糖化血红蛋白A1c （HbA1c）和肌酐、自我报告的运动和体重指数相关。控制年龄和性别，较高的HDL （HR 0.84, 95% CI 0.73至0.96,p=0.010）和apoA1 （HR 0.83, 95% CI 0.72至0.94,p=0.005）与ALS风险降低相关。较高的总胆固醇：HDL与ALS风险增加相关（HR 1.17, 95% CI 1.05 ~ 1.31, p=0.006）。在包含多种代谢标志物的模型中，高LDL或载脂蛋白ob与ALS风险增加相关，此外，高HDL或载脂蛋白a的风险较低。冠状动脉疾病、脑血管疾病和年龄的增长也与ALS的风险增加有关。HDL、apoA1和LDL水平与ALS发病风险的关联提供了越来越多的证据，表明发病前代谢环境可能在发病机制中发挥作用。了解这些变化的分子基础将为症状前生物标志物的开发和治疗靶向提供信息。
Premorbid body mass index, physical activity, diabetes and cardiovascular disease have been associated with an altered risk of developing amyotrophic lateral sclerosis (ALS). There is evidence of shared genetic risk between ALS and lipid metabolism. A very large prospective longitudinal population cohort permits the study of a range of metabolic parameters and the risk of subsequent diagnosis of ALS. The risk of subsequent ALS diagnosis in those enrolled prospectively to the UK Biobank (n=502 409) was examined in relation to baseline levels of blood high and low density lipoprotein (HDL, LDL), total cholesterol, total cholesterol:HDL ratio, apolipoproteins A1 and B (apoA1, apoB), triglycerides, glycated haemoglobin A1c (HbA1c) and creatinine, plus self-reported exercise and body mass index. Controlling for age and sex, higher HDL (HR 0.84, 95% CI 0.73 to 0.96, p=0.010) and apoA1 (HR 0.83, 95% CI 0.72 to 0.94, p=0.005) were associated with a reduced risk of ALS. Higher total cholesterol:HDL was associated with an increased risk of ALS (HR 1.17, 95% CI 1.05 to 1.31, p=0.006). In models incorporating multiple metabolic markers, higher LDL or apoB was associated with an increased risk of ALS, in addition to a lower risk with higher HDL or apoA. Coronary artery disease, cerebrovascular disease and increasing age were also associated with an increased risk of ALS. The association of HDL, apoA1 and LDL levels with risk of ALS contributes to an increasing body of evidence that the premorbid metabolic landscape may play a role in pathogenesis. Understanding the molecular basis for these changes will inform presymptomatic biomarker development and therapeutic targeting.
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影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
3.7
作者：
Horrocks S;Wilkinson T;Schnier C;Ly A;Woodfield R;Rannikmäe K;Quinn TJ;Sudlow CL
通讯作者：
Sudlow CL
DOI：
10.1136/jnnp.2009.183525
发表时间：
2010-04
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Logroscino G;Traynor BJ;Hardiman O;Chiò A;Mitchell D;Swingler RJ;Millul A;Benn E;Beghi E;EURALS
通讯作者：
EURALS
影响因子：
2.9
作者：
Bradbury, Kathryn E.;Guo, Wenji;Key, Timothy J.
通讯作者：
Key, Timothy J.
影响因子：
1.2
作者：
Ikeda, Ken;Hirayama, Takehisa;Iwasaki, Yasuo
通讯作者：
Iwasaki, Yasuo