Enhanced lymphotoxin alpha DNA hypermethylation and correlation with genetic polymorphism in rheumatoid arthritis...

Rheumatoid arthritis (RA) is a multifactorial autoimmune disorder characterized by persistent inflammation and joint destruction. Despite advances in understanding RA's immunopathology, its epigenetic regulation remains underexplored, particularly in diverse populations. This study aims to bridge this gap by examining lymphotoxin alpha (LTA) DNA methylation in a Chinese cohort and exploring the relationship with gene polymorphism.

This study involved 145 RA patients and 140 age-matched healthy controls from Qingdao, China. We analyzed DNA methylation in the LTA gene using bisulfite sequencing and assessed SNP genotypes with high-resolution melting analysis. Statistical correlations were performed using SPSS to link methylation patterns with clinical indicators of RA severity.

Significantly higher methylation levels were observed at several CpG sites within the LTA gene in RA patients compared to controls. These methylation patterns were positively correlated with clinical measures such as erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score-28, suggesting their relevance in RA pathophysiology. The CC genotype of rs2009658 was associated with elevated methylation at multiple CpG sites within the LTA gene, as well as the TT genotype of rs2229094.

LTA DNA methylation is a potential inflammatory indicator and therapeutic target for RA. The rs2009658 CC genotype and rs2229094 TT genotype are susceptible genotypes associated with LTA hypermethylation.