Genomic (epigenetic) DNA methylation in patients with open‐angle glaucoma

Abstract

Abstract Purpose DNA methylation occurs by transfer of a methyl group to cytosine residues in the CpG1 islands. The extent of DNA methylation positively correlates with the extent of gene inactivation. The present study was performed to investigate whether there is an altered global DNA methylation in patients with open‐angle glaucoma. Methods This prospectice case control study included 59 patients 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). 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 with a modified non‐radioactive assay. Statistics: Mann‐Whitney‐Test (2‐tailed), the results are presented as means (SD), significance level p<0.05. 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. Conclusion Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have 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.