RT Journal Article
SR Electronic
T1 Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 527
OP 532
DO 10.1136/ard-2022-222796
VO 82
IS 4
A1 Nam, Bora
A1 Jo, Sungsin
A1 Bang, So-Young
A1 Park, Youngho
A1 Shin, Ji Hui
A1 Park, Ye-Soo
A1 Lee, Seunghun
A1 Joo, Kyung Bin
A1 Kim, Tae-Hwan
YR 2023
UL http://ard.bmj.com/content/82/4/527.abstract
AB Objectives To identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS).Methods We newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To identify clinical and genetic factors associated with severe radiographic damage, multiple linear regression analyses were performed. Human AS-osteoprogenitor and control-osteoprogenitor cells were used for functional validation.Results The significant clinical factors of final mSASSS were baseline mSASSS (β=0.796, p=3.22×10−75), peripheral joint arthritis (β=−0.246, p=6.85×10−6), uveitis (β=0.157, p=1.95×10−3), and smoking (β=0.130, p=2.72×10−2) after adjusting for sex, age and disease duration. After adjusting significant clinical factors, the Ryanodine receptor 3 (RYR3) gene was associated with severe radiographic damage (p=1.00×10−6). For pathway analysis, the PI3K-Akt signalling pathway was associated with severe radiographic damage in AS (p=2.21×10−4, false discovery rate=0.040). Treatment with rhodamine B, a ligand of RYR3, dose-dependently induced matrix mineralisation of AS osteoprogenitors. However, the rhodamine B-induced accelerated matrix mineralisation was not definitive in control osteoprogenitors. Knockdown of RYR3 inhibited matrix mineralisation in SaOS2 cell lines.Conclusions This study identified clinical and genetic factors that contributed to better understanding of the pathogenesis and biology associated with radiographic damage in AS.Data are available upon reasonable request.