Centre for Rheumatology and Clinical Immunology, and Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland.
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
Ann Rheum Dis. 2021 Dec;80(12):1530-1536. doi: 10.1136/annrheumdis-2021-220698. Epub 2021 Aug 3.
To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a promoter variant.
FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a promoter variant.
Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for carriers and 6.1% (95% CI: 5.0% to 7.2%) for non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men.
Our findings provide estimates of lifetime risk of RA-ILD based on mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.
针对最强已知的肺纤维化风险因素——一个启动子变异，估计类风湿关节炎相关间质性肺病（RA-ILD）的终生发病风险。
FinnGen 是一个流行病学队列和医院生物样本库的集合，在芬兰全国登记处将遗传数据与长达 50 年的随访相结合。RA 和 ILD 患者从芬兰国家住院、药物报销和死因登记处确定。我们根据常见变体 rs35705950（一个启动子变体），估计了 80 岁时 ILD 的终生发病风险。
在 293972 名个体中，1965 名（0.7%）在 80 岁时发展为 ILD。在数据集的所有个体中，该变体增加了 ILD 的风险，HR 为 2.44（95%CI：2.22 至 2.68）。在 6869 名被诊断为 RA 的患者中，247 名（3.6%）发展为 ILD。在 RA 患者中，该变体是 ILD 的一个强烈风险因素，HR 与全数据集相似（HR：2.27，95%CI：1.75 至 2.95）。在 RA 患者中，ILD 的终生发病风险为 16.8%（95%CI：13.1%至 20.2%），携带者为 16.8%，非携带者为 6.1%（95%CI：5.0%至 7.2%）。风险之间的差异在 65 岁时开始显现，男性风险更高。
我们的研究结果提供了基于 突变载体状态的 RA-ILD 终生发病风险的估计，证明了基因组学在 RA-ILD 风险分层中的潜力。
