PT  - JOURNAL ARTICLE
AU  - Bora Nam
AU  - Sungsin Jo
AU  - So-Young Bang
AU  - Youngho Park
AU  - Ji Hui Shin
AU  - Ye-Soo Park
AU  - Seunghun Lee
AU  - Kyung Bin Joo
AU  - Tae-Hwan Kim
TI  - Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis
AID  - 10.1136/ard-2022-222796
DP  - 2023 Apr 01
TA  - Annals of the Rheumatic Diseases
PG  - 527--532
VI  - 82
IP  - 4
4099  - http://ard.bmj.com/content/82/4/527.short
4100  - http://ard.bmj.com/content/82/4/527.full
SO  - Ann Rheum Dis2023 Apr 01; 82
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.