Association of CD8 + + T‐cells with bone erosion in patients with rheumatoid arthritis

摘要

Abstract Aim Bone erosion is a major problem worsening quality of rheumatoid arthritis ( RA ) patients’ lives. However, causal factors responsible for bone erosion in RA have remained unclear. We aimed to examine genetic variants conferring bone erosion in RA using a Korean genome‐wide association study ( GWAS ) and to search for possible biological mechanisms underlying the development of bone erosion. Method We obtained genome‐wide single nucleotide polymorphism ( SNP ) data for 711 Korean RA patients using Illumina HapMap 550v3/660W arrays. Associations between SNP s and bone erosion status based on the Steinbrocker staging system were examined using multivariate logistic regression. Cell‐type‐specific enrichment of the epigenomic chromatin annotation H3K4me3 at the bone erosion associated variants was further investigated using National Institute of Health Roadmap Epigenomics data. Results As we tested the associations between 439 289 SNP s and bone erosion in 385 patients with erosive RA and 326 with non‐erosive RA , none of the tested SNP s reached the genome‐wide significance threshold, although many loci showed modest genetic effect on bone erosion status with suggestive association (e.g., rs2741200 [ P = 3.75 × 10 ?6 ] in the SLA ‐ TG locus and rs12422918 [ P = 4.13 × 10 ?6 ] in SRGAP 1 ). However, the top‐ranked SNP s and their linked proxies, which were mostly located in non‐coding variants, were significantly co‐localized with the highly tissue‐specific regulatory marker H3K4me3 in CD8 + memory T‐cells ( P = 0.014). Conclusion Although, there was no large‐effect variants associated with bone erosion in our GWAS , we have shown that CD8 + memory T‐cells may have relevance with bone erosion in patients with RA through the analysis of ChiP‐seq data.