Alteration of serum bile acids in amyotrophic lateral sclerosis.
Alteration of serum bile acids in amyotrophic lateral sclerosis.
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DOI：
10.1002/lipd.12390
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发表时间：
2024-02
期刊：
影响因子：
1.9
通讯作者：
Ikjae Lee;Renu Nandakumar;Rebecca A. Haeusler
中科院分区：
文献类型：
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作者：
Ikjae Lee;Renu Nandakumar;Rebecca A. Haeusler
亲水性内源性胆汁酸熊去氧胆酸（UDCA）、牛磺熊去氧胆酸（TUDCA）和葡萄糖尿脱氧胆酸（GUDCA）具有神经保护作用。我们进行了一项病例对照研究，以检查ALS诊断和血清胆汁酸水平之间的关系。包括散发性和家族性ALS患者，年龄和性别匹配的健康对照，以及捐献血液样本的前驱基因携带者。将储存在-80 ° C下的非禁食血清样品用于分析。采用液相色谱-质谱法（LC-MS）测定血清胆汁酸水平。获得15种胆汁酸的浓度，5种非结合型和10种结合型，并使用Wilcoxon-Rank-Sum检验比较ALS与对照组（症状前基因携带者+健康对照）。共纳入80名参与者：31名ALS（17名散发性ALS和14名家族性ALS）; 49名对照（22名基因携带者，27名健康对照）。平均年龄为50岁，50%为男性。在ALS组中，45%的人患有家族性疾病，其中C9 orf 72（29%），TARDBP（10%），FUS（3%）和CHCHD 10（3%）基因中存在致病性变异。在对照组中，43%携带致病性变体：C9 orf 72（27%），SOD 1（10%）和FUS（6%）。与对照组相比，ALS组中UDCA、TUDCA和GUDCA的血清水平有升高趋势（中位数分别为27与7 nM、4与3 nM、110与47 nM，p值分别为0.04、0.06、0.04）。其他胆汁酸血清水平无显著组间差异。总之，与对照组相比，ALS患者血清UDCA、TUDCA、GUDCA水平呈升高趋势，未发现缺陷证据。
Hydrophilic endogenous bile acids ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), and glucourosodeoxycholic acid (GUDCA) have suggested neuroprotective effects. We performed a case-control study to examine the association between ALS diagnosis and serum levels of bile acids. Sporadic and familial ALS patients, age- and sex-matched healthy controls, and presymptomatic gene carriers who donated blood samples were included. Non-fasted serum samples stored at -80°C were used for the analysis. Serum bile acid levels were measured by liquid chromatography-mass spectrometry (LC-MS). Concentrations of 15 bile acids were obtained, 5 non-conjugated and 10 conjugated, and compared between ALS versus control groups (presymptomatic gene carriers + healthy controls) using the Wilcoxon-Rank-Sum test. In total, 80 participants were included: 31 ALS (17 sporadic and 14 familial ALS); 49 controls (22 gene carriers, 27 healthy controls). The mean age was 50 years old and 50% were male. In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes. In the control group, 43% carried pathogenic variants: C9orf72 (27%), SOD1 (10%), and FUS (6%). The serum levels of UDCA, TUDCA, and GUDCA trended higher in the ALS group compared to controls (median 27 vs. 7 nM, 4 vs. 3 nM, 110 vs. 47 nM, p-values 0.04, 0.06, 0.04, respectively). No significant group differences were found in other bile acids serum levels. In conclusion, the serum level of UDCA, TUDCA, GUDCA trended higher in ALS patients compared to controls, and no evidence of deficiencies was found.