Department of Public Health and Medicine/Rheumatology, Umeå University, Umeå.
Department of Medical Sciences, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory.
Rheumatology (Oxford). 2022 Mar 2;61(3):943-952. doi: 10.1093/rheumatology/keab441.
Pulmonary manifestations in RA are common comorbidities. Interstitial lung disease (ILD), both idiopathic and in RA, has been associated with several genetic variants. We assessed pulmonary fibrosis (PF) in an inception cohort of RA patients in relation to genetic variants and disease-related factors.
A total of 1466 early RA patients were consecutively included and followed prospectively from the index date until death or 31 December 2016. Clinical and laboratory data and treatment were continuously registered according to the Swedish Rheumatology Quality Register. DNA was available from 1184 patients and 571 151 genome-wide single-nucleotide polymorphisms (SNPs) were analysed. Thirteen identified genetic variants were extracted. At follow-up, the patients answered a questionnaire regarding disease progression and lung involvement that was validated by reviewing medical records and analysing radiological examinations.
The prevalence of PF was 5.6% and the annualized incidence rate was 5.0/1000 (95% CI 3.80, 6.54). Four SNPs were associated with PF in RA: rs35705950 [MUC5B; OR 2.5 (95% CI 1.5, 4.0), adjusted P-value = 0.00016, q-value = 0.0021]; rs111521887 [TOLLIP; OR 1.9 (95% CI 1.3, 2.8), adjusted P-value = 0.0014, q-value = 0.0092]; rs2609255 [FAM13A; OR 1.7 (95% CI 1.1, 2.5), adjusted P-value = 0.013, q-value = 0.055] and rs2736100 [TERT; OR 1.5 (95% CI 1.0, 2.2), adjusted P-value = 0.046, q-value = 0.15]. Older age and RF positivity were associated with increased risk, while MTX treatment was associated with a lower risk of PF.
Development of PF in an inception cohort of RA patients was associated with 4 of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF positivity were of limited importance in PF development.
类风湿关节炎（RA）的肺部表现是常见的合并症。特发性和 RA 相关的间质性肺疾病（ILD）与多种遗传变异有关。我们评估了 RA 患者队列中与遗传变异和疾病相关因素有关的肺纤维化（PF）。
共连续纳入 1466 例早期 RA 患者，并从索引日期开始前瞻性随访，直至死亡或 2016 年 12 月 31 日。临床和实验室数据以及治疗方法按照瑞典风湿病质量登记处进行连续登记。1184 例患者的 DNA 可用，分析了 571151 个全基因组单核苷酸多态性（SNP）。提取了 13 个已确定的遗传变异。在随访中，患者回答了一份关于疾病进展和肺部受累的问卷，该问卷通过查阅病历和分析影像学检查进行了验证。
PF 的患病率为 5.6%，年发病率为 5.0/1000（95%CI 3.80，6.54）。四个 SNP 与 RA 中的 PF 相关：rs35705950[MUC5B；OR 2.5（95%CI 1.5，4.0），调整后的 P 值=0.00016，q 值=0.0021]；rs111521887[TOLLIP；OR 1.9（95%CI 1.3，2.8），调整后的 P 值=0.0014，q 值=0.0092]；rs2609255[FAM13A；OR 1.7（95%CI 1.1，2.5），调整后的 P 值=0.013，q 值=0.055]和 rs2736100[TERT；OR 1.5（95%CI 1.0，2.2），调整后的 P 值=0.046，q 值=0.15]。年龄较大和 RF 阳性与风险增加相关，而 MTX 治疗与 PF 风险降低相关。
在 RA 患者的起始队列中，PF 的发展与 12 个 ILD 风险基因中的 4 个相关。除了诊断时的年龄和 RF 阳性外，RA 相关因素在 PF 发展中的重要性有限。
