Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus

Genes Genomics. 2023 Sep;45(9):1187-1196. doi: 10.1007/s13258-023-01407-4. Epub 2023 Jun 10.

Abstract

Background: As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood.

Objective: We aimed to investigate the possible significance of SLE's DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets.

Methods: We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people.

Results: 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE.

Conclusions: Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

Keywords: DNA methylation; Epigenetics; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • DNA Methylation / genetics
  • Humans
  • Lupus Erythematosus, Systemic* / genetics
  • src-Family Kinases* / genetics
  • src-Family Kinases* / metabolism

Substances

  • hydrogen sulfite
  • src-Family Kinases
  • Biomarkers