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@ARTICLE{Xia:165272,
author = {Xia, Kailin and Witzel, Simon and Witzel, Christina and
Klose, Veronika and Fan, Dongsheng and Ludolph, Albert C and
Dorst, Johannes},
title = {{M}utation-specific metabolic profiles in presymptomatic
amyotrophic lateral sclerosis.},
journal = {European journal of neurology},
volume = {30},
number = {1},
issn = {1351-5101},
address = {Oxford},
publisher = {Blackwell Science},
reportid = {DZNE-2022-01565},
pages = {87-95},
year = {2023},
note = {ISSN 1468-1331 not unique: **2 hits**.},
abstract = {Growing evidence shows that ALS patients feature a
disturbed energy metabolism. However, these features have
rarely been investigated in the presymptomatic stage.A total
of 60 presymptomatic ALS mutation carriers and 70 age- and
gender-matched controls (non-mutation carriers from the same
families) were recruited. All subjects underwent assessments
of their metabolic profiles under fasting conditions at
enrollment, including body mass index (BMI), blood pressure
and serum levels of blood glucose, total cholesterol,
triglycerides, high-density lipoprotein (HDL) and
low-density lipoprotein.All mutations combined, no
differences between presymptomatic ALS gene carriers and
controls were found. From a cardiovascular point of view,
presymptomatic chromosome 9 open reading frame 72 (C9ORF72)
gene carriers showed lower cardiovascular risk profiles
compared to healthy controls, including lower BMI (median
22.9, interquartile range [IQR] 20.6-26.1 kg/m2 vs. 24.9,
IQR 22.7-30.5 kg/m2 ; p = 0.007), lower systolic blood
pressure (120, IQR 110-130 mmHg vs. 128, IQR 120-140 mmHg; p
= 0.02), lower fasting serum glucose (89.0, IQR 85.0-97.0
mg/dl vs. 96.0, IQR 89.3-102.0 mg/dl; p = 0.005) and higher
HDL (1.6, IQR 1.3-1.8 mmol/l vs. 1.2, IQR 1.0-1.4 mmol/l; p
= 0.04). However, presymptomatic superoxide dismutase 1
(SOD1) gene mutation carriers showed higher cardiovascular
risk profiles compared to healthy controls, including higher
BMI (28.0, IQR 26.1-31.5 kg/m2 vs. 24.9, IQR 22.7-30.5 kg/m2
; p = 0.02), higher fasting serum glucose (100.0, IQR
94.0-117.0 mg/dl vs. 96.0, IQR 89.3-102.0 mg/dl; p = 0.04)
and lower HDL (1.2, IQR 1.0-1.4 mmol/l vs. 1.4, IQR 1.2-1.7
mmol/l; p = 0.01). These features were most prominent in
patients carrying SOD1 gene mutations associated with slow
disease progression.This study identified distinct metabolic
profiles in presymptomatic ALS gene carriers, which might be
associated with disease progression in the symptomatic
phase.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: genetics /
Superoxide Dismutase-1: genetics / Blood Glucose / Disease
Progression / Metabolome / Amyotrophic lateral sclerosis
(Other) / Genetics (Other) / Metabolism (Other) /
Presymptomatic Gene Carriers (Other)},
cin = {Clinical Study Center Ulm / AG Zhan},
ddc = {610},
cid = {I:(DE-2719)5000077 / I:(DE-2719)1910005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36169607},
doi = {10.1111/ene.15584},
url = {https://pub.dzne.de/record/165272},
}