Abstract
Purpose:
DNA methylation occurs by transfer of a methyl group to cytosine residues in the dinucleotide sequence CpG. The extent of DNA methylation positively correlates with the extent of gene inactivation. The disruption of the heritable methylation patterns in DNA can lead to alterations in chromatin structure and alterations in gene expression promoting chronic diseases. The present study was performed to investigate whether there is an altered global DNA methylation in patients with open-angle glaucoma.
Methods:
59 patients from the Erlangen Glaucoma Registry Erlangen Glaucoma Registry, ISSN 2191-5008, CS-2011; NTC00494923) with primary open-angle glaucoma (POAG, age: 68 (SD 8) years), 54 patients with secondary open-angle glaucoma due to pseudoexfoliation syndrome (PEXG, age: 72 (SD 8) years), and 53 patients with cataract as controls (age: 69 (SD 11) years) were included. Total DNA was extracted from frozen EDTA-blood using QIAmp DNA Blood Mini Kit (Qiagen). Global methylation status [DNA methylation in %, 1-(HpaII/MspI)] was measured according to Pogribny et al. (Biochem Biophys Res Commun. 1999; 262:624-8) with a modified non-radioactive assay5. Statistics: Comparisons were made using the Mann-Whitney-Test (2-tailed) and the results are presented as means (SD). A p-value of less than 0.05 was considered significant.
Results:
There was a significantly elevated genomic DNA methylation (in %) 1-(HpaII/MspI) in peripheral mononuclear cells in patients with POAG (68%, SD 18; U=868, Z = -2.79, p=0.005), but not in PEXG (55%, SD 17; U=1049, Z=-0.57, p=0.57) when compared with healthy controls (55%, SD 24). Thus, the difference between POAG and PEXG was exactly 13% of methylated HpaII/MspI restriction sites.
Conclusions:
Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control in patients with POAG. Further studies including gene-specific analyses are needed to clarify the differences between POAG and PEXG.
Keywords: 539 genetics •
629 optic nerve •
636 pathobiology