Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Brain Res. 2022 Oct 1;1792:148022. doi: 10.1016/j.brainres.2022.148022. Epub 2022 Jul 22.
DNA methylation has been identified to play an important role in amyotrophic lateral sclerosis (ALS). Galectin-1, encoded by LGALS1 gene, has been proved to be associated with ALS. We aimed to investigate the association between the expression and methylation of LGALS1 in blood samples from ALS patients.
Forty-five patients diagnosed with ALS were enrolled. Thirty-two healthy relatives consisted the control group. Among them, samples from 12 patients and 12 controls consisted the exploration samples. In the exploration samples, mRNA expression levels were detected by quantitative real-time PCR. In all the samples, DNA methylation levels of one CpG island containing 12 CpG sites in the gene promoter were detected by bisulfite sequencing PCR, and galectin-1 levels were examined by enzyme linked immunosorbent assay. Associations between the gene expression and methylation level, as well as between the region-specific methylation level and clinical variables were calculated.
The mRNA expression level of LGALS1 was significantly increased and the promoter of LGALS1 was hypomethylated in ALS patients. Serum galectin-1 levels were significantly elevated in the ALS patients. The ALS group had significantly lower methylation level at certain CpG sites than the control group. There were significant negative associations between abnormal expression and methylation of LGALS1, as well as between region-specific methylation levels and the age of onset.
The aberrant expression and DNA methylation of LGALS1 and their association reveals epigenetic changes in ALS patients, which are helpful for early intervention and treatment for the disease.
DNA 甲基化在肌萎缩侧索硬化症（ALS）中起着重要作用。半乳糖凝集素-1（Galectin-1）由 LGALS1 基因编码，已被证明与 ALS 有关。我们旨在研究 ALS 患者血液样本中 LGALS1 的表达和甲基化之间的关联。
共纳入 45 名确诊为 ALS 的患者。32 名健康亲属为对照组，其中 12 名患者和 12 名对照组成探索样本。在探索样本中，采用实时定量 PCR 检测 mRNA 表达水平。在所有样本中，采用亚硫酸氢盐测序 PCR 检测基因启动子中包含 12 个 CpG 位点的一个 CpG 岛的 DNA 甲基化水平，并采用酶联免疫吸附试验检测半乳糖凝集素-1 水平。计算基因表达与甲基化水平之间，以及特定区域甲基化水平与临床变量之间的相关性。
ALS 患者的 LGALS1 mRNA 表达水平显著升高，LGALS1 启动子呈低甲基化状态。ALS 患者的血清半乳糖凝集素-1 水平显著升高。与对照组相比，ALS 组在某些 CpG 位点的甲基化水平显著降低。LGALS1 异常表达与甲基化之间，以及特定区域甲基化水平与发病年龄之间存在显著负相关。
LGALS1 的异常表达和 DNA 甲基化及其相关性揭示了 ALS 患者的表观遗传变化，有助于对该疾病进行早期干预和治疗。
