RESUMO
DNA methylation may predispose to multiple sclerosis (MS), as aberrant methylation in the promoter regions across the genome seems to underlie several processes of MS. We have currently determined the methylation status of eight genes in relapsing-remitting MS patients. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to determine the status of 31 CpG islands, located across eight genes, in 33 healthy individuals and 66 MS patients (33 in relapse and 33 in remission). The methylation levels in the examined sites ranged from 0 to 31%. Methylation positivity for RUNX3 and CDKN2A differed significantly between MS patients and healthy controls. Maximum methylation in RUNX3, CDKN2A, SOCS1, and NEUROG1 genes was significantly different between patients and controls. Roc curves demonstrated that the appropriate cut-offs to distinguish patients from healthy controls were 2% for RUNX3 (OR 3.316, CI 1.207-9.107, p = 0.024) and 3% for CDKN2A (OR 3.077, CI 1.281-7.39, p = 0.018). No difference in methylation was observed between patients in relapse and patients in remission, in any of the genes examined. Methylation patterns of RUNX3 and CDKN2A may be able to distinguish between MS patients and healthy controls, but not between MS patients in relapse and in remission. Graphical Abstract Methylation patterns of RUNX3 and CDKN2A may be able to discriminate healthy individuals from MS patients.
Assuntos
Ilhas de CpG , Metilação de DNA , Esclerose Múltipla Recidivante-Remitente/genética , Adolescente , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Proteínas do Tecido Nervoso/genética , Proteína 1 Supressora da Sinalização de Citocina/genéticaRESUMO
Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues.
