Hypomethylation of The Low-density Lipoprotein Receptor Class A Domain Containing 4 Gene in Rheumatoid Arthritis in a Chinese population

Abstract

Background: Rheumatoid arthritis, a chronic inflammatory disease, is characterized by destruction of synovial joints. The pathogenesis of RA is unclear, and DNA methylation plays important roles in the expression of related genes. LDLRAD4 is identified from three GWAS, in which the expression of LDLRAD4 was different in RA. LDLRAD4functions as a negative regulator of TGF-β signaling, which affects cell proliferation, differentiation and apoptosis. There are few studies on the correlation between LDLRAD4 methylation and RA, and this study aims to investigate the relationship in Chinese population. Methods and Results: Clinical information and peripheral blood samples of 150 RA and 150 healthy controls were collected, and DNA methylation levels of LDLRAD4 gene and CpG sites were detected. Hypomethylation of LDLRAD4 genewas observed in RA patients, especially LDLRAD4-43F and LDLRAD4-44F regions. The AUC value of LDLRAD4-44F region was 0.78 to predict disease. In RF+/CCP- group, methylation levels of LDLRAD4, LDLRAD4-42-1F, LDLRAD4-43F and LDLRAD4-44F regions were strongly correlated withDAS28, ESR and CRP, while in RF-/CCP+ group, LDLRAD4-42-2F region was strongly correlated with ESR and CRP. Conclusions: LDLRAD4 methylation is a potential diagnostic and inflammatory indicator of RA.