Klein Jacob, Wheeler Austin, Baker Joshua F, Yang Yangyuna, Roul Punyasha, Frideres Halie, Wysham Katherine D, Kerr Gail S, Reimold Andreas, Ascherman Dana P, Kunkel Gary A, Cannon Grant W, Monach Paul A, Poole Jill A, Thiele Geoffrey M, Mikuls Ted R, England Bryant R
Division of Rheumatology & Immunology, VA Nebraska Western Iowa Health Care System & University of Nebraska Medical Center, Omaha, NE.
Corporal Michael J. Crescenz VA Medical Center and University of Pennsylvania, Philadelphia, PA.
Rheumatology (Oxford). 2024 Nov 6. doi: 10.1093/rheumatology/keae615.
Investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD).
We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or end of study period. The MUC5B rs35705950 promoter variant was measured using an Infinium genotyping array, assuming autosomal dominant inheritance. Survival and cause of death were determined from VA death records and the National Death Index. Associations of the MUC5B promoter variant with survival were tested in Cox regression models adjusting for potential confounders.
Among 263 participants with RA-ILD (mean age 69 years, 95% male, 73% white race, 85% smoking history), the MUC5B promoter variant was present in 33.5%. Mortality rate was similar between those with (12.2/100PY [95% CI: 9.4, 15.8]) and without (11.1/100PY [95% CI: 9.1, 13.5]) the variant. MUC5B status was not significantly associated with survival overall (aHR 0.97 [95% CI: 0.68, 1.37]) or when stratified by ILD pattern (clinical usual interstitial pneumonia [UIP] aHR 0.86 [95% CI: 0.55, 1.35]; clinical non-UIP aHR 1.15 [95% CI: 0.63, 2.09]). Further, MUC5B status was not significantly associated with respiratory-related (aHR 0.83 [95% CI: 0.42, 1.66]) or non-respiratory causes of death (aHR 1.08 [95% CI: 0.72, 1.62]).
While associated with RA-ILD risk, the MUC5B promoter variant was not predictive of survival among RA-ILD patients in this multicentre cohort. Further studies are needed to identify other genetic and non-genetic prognostic factors in RA-ILD to inform disease management.
研究黏蛋白5B（MUC5B）rs35705950启动子变异与类风湿关节炎相关间质性肺病（RA-ILD）患者生存率之间的关联。
我们对退伍军人事务部类风湿关节炎（VARA）登记处中确诊为ILD的参与者进行了研究。对参与者进行随访直至死亡或研究期结束。使用Infinium基因分型芯片检测MUC5B rs35705950启动子变异，假设其为常染色体显性遗传。从退伍军人事务部死亡记录和国家死亡指数中确定生存率和死亡原因。在调整潜在混杂因素的Cox回归模型中测试MUC5B启动子变异与生存率之间的关联。
在263例RA-ILD患者中（平均年龄69岁，95%为男性，73%为白人，85%有吸烟史），33.5%存在MUC5B启动子变异。有该变异者（12.2/100人年[95%置信区间：9.4，15.8]）和无该变异者（11.1/100人年[95%置信区间：9.1，13.5]）的死亡率相似。MUC5B状态与总体生存率（风险比0.97[95%置信区间：0.68，1.37]）或按ILD模式分层时均无显著关联（临床普通型间质性肺炎[UIP]风险比0.86[95%置信区间：0.55，1.35]；临床非UIP风险比1.15[95%置信区间：0.63，2.09]）。此外，MUC5B状态与呼吸相关死亡原因（风险比0.83[95%置信区间：0.42，1.66]）或非呼吸相关死亡原因（风险比1.08[95%置信区间：0.72，1.62]）均无显著关联。
虽然MUC5B启动子变异与RA-ILD风险相关，但在这个多中心队列中，它并不能预测RA-ILD患者的生存率。需要进一步研究以确定RA-ILD中其他遗传和非遗传预后因素，为疾病管理提供依据。
