PDF(Pubmed)
Abstract：
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.
摘要：
亲水性内源性胆汁酸熊去氧胆酸（UDCA），牛磺熊去氧胆酸（TUDCA），和葡糖脱氧胆酸（GUDCA）已经提出了神经保护作用。我们进行了一项病例对照研究，以检查ALS诊断与血清胆汁酸水平之间的关系。散发性和家族性ALS患者，年龄和性别匹配的健康对照，包括捐献血液样本的症状前基因携带者。在-80°C下储存的未禁食的血清样品用于分析。采用液相色谱-质谱(LC-MS)法测定血清胆汁酸水平。获得15种胆汁酸的浓度，5个非共轭和10个共轭，并使用Wilcoxon-Rank-Sum检验在ALS与对照组（症状前基因携带者+健康对照）之间进行比较。总的来说,包括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个健康对照）。平均年龄为50岁，50%为男性。在ALS组中,45％患有C9orf72致病变异的家族性疾病（29％），TARDBP(10%),FUS（3%），和CHCHD10(3%)基因。在对照组中，43%携带致病性变异：C9orf72(27%)，SOD1（10%），和FUS（6%）。UDCA的血清水平，TUDCA,与对照组相比，ALS组的GUDCA趋势更高(中位数27vs.7nM,4vs.3nM,110vs.47nM,p值分别为0.04、0.06、0.04)。其他胆汁酸血清水平无明显差异。总之,UDCA的血清水平，TUDCA,与对照组相比，ALS患者的GUDCA趋势更高，没有发现缺陷的证据。
