Association between abnormal expression and methylation of LGALS1 in amyotrophic lateral sclerosis.

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.