Global hypomethylation pattern in systemic sclerosis: An application for absolute quantification of epigenetic DNA modification products by 2D-UPLC-MS/MS


Dal-Bekar N. E., Siomek-Gorecka A., Gackowski D., KÖKEN AVŞAR A., YARKAN TUĞSAL H., BİRLİK A. M., ...Daha Fazla

CLINICAL IMMUNOLOGY, cilt.239, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 239
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.clim.2022.108997
  • Dergi Adı: CLINICAL IMMUNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: DNA methylation, DNA demethylation, Epigenetics, Systemic sclerosis, 2D-UPLC-MS/MS, PATHOGENESIS, METHYLATION
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Besides genetics risk factors, understanding the epigenetic modifications in SSc has been gaining acceleration in recent years. Epigenetic modifications are reversible and defined as druggable targets. In this context, it is highly important to present a systemic perspective to epigenetic modifications of SSc in terms of both pathogenesis and clinical utility. Material and methods: DNA samples from the whole blood specimens of the 41 SSc patients and 27 healthy controls (HCs) were obtained. Absolute quantification of 5-mC, 5-hmdC, 5-cadC, 5-fdC, and 5-hmdU as the DNA methylation and demethylation products were performed using 2D-UPLC-MS/MS. Demographic data and clinical scores were recorded in detail. Results: 5-hmdU was significantly higher in SSc patients while 5-hmdC was lower compared to the HCs (p < 0.01, p = 0.012 respectively). 5-cadC and 5-fdC had upward trend in SSc (p = 0.064; p = 0.066). These results support that SSc patients tend to have a global hypomethylation pattern. Clinical analyzes revealed that lung, gastrointestinal, joint, and vascular involvement of SSc is also associated with increased demethylation or decreased methylation profile. Conclusion: We performed absolute quantification of epigenetic DNA modification products in SSc for the first time. We demonstrated an upward trend in global hypomethylation in SSc. Furthermore, as a result of detailed clinical analyzes, the relationship between lung, GIS, and vascular involvement with epigenetic changes was shown. We believe that absolute quantification of DNA methylation and demethylation products with novel technologies can provide a deep understanding of disease pathogenesis and has the potential to mark an era for developing new therapeutic strategies.