engleski

Global DNA hypomethylation in white blood cells represents a feature of multiple sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory disease of a central nervous system. It is thought that both, hereditary and environmental factors contribute to the elevated risk for the disease occurrence. Environmental factors that are associated with epigenom modification, such as vitamin D level, smoking, Epstein-Barr virus (EBV) infection and diet were showed to impact the MS risk. DNA methylation, a process that involves adding of methyl group to the C5 position of cytosine in C-G dinucleotides, is the most studied epigenetic mechanism. The majority of CpG dinucleotides are found in repeated sequences such as Long Interspersed Nucleotide Element (LINE) family. The majority of them are truncated but so-called LINE-1, which comprised nearly 17% of human genome, can be transcribed. LINE-1 methylation correlates with global DNA methylation. The aim of this study was to determine whether there were differences in the global DNA methylation in white blood cells between MS patients and healthy controls. We collected blood samples from 36 Croatian patients with MS and 100 healthy control females. After DNA isolation we performed the sodium bisulphite modification. Global DNA methylation was assessed by quantifying the methylation of LINE-1 elements using the real time methylation specific PCR (Methylight). We used Alu-based real-time PCR control reaction in order to normalized DNA input. The MethyLight data specific for methylated repetitive elements were expressed as percent of methylated reference (PMR) values, while the levels of unmethylated repetitive elements were expressed as percent of unmethylated reference (PUR) values. Our results showed that the methylation level of LINE-1 elements was significantly reduced in MS patients compared to the healthy controls (M-W U test ; p<0.05). Neither gender nor age was found to be associated with the LINE-1 methylation level in patients or controls. Based on our findings, we can conclude that patients with MS display global DNA hypomethylation in white blood cells. Since, peripheral blood is easily accessible, measurement of LINE-1 methylation in white blood cells could be used in future for the development of prospective new biomarkers for MS. Still, it remains unknown weather this hypomethylation is the cause or the consequence of the disease and this will be the subject of our future research.

Global DNA methylation; Multiple sclerosis

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