Objective Investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD). Methods 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. Results 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]). Conclusion 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.

中文翻译：

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类风湿性关节炎相关间质性肺病的 MUC5B 启动子变异和生存率


目的 探讨 MUC5B rs35705950 启动子变异与 RA 相关间质性肺病 （RA-ILD） 生存率的相关性。方法 我们研究了退伍军人事务类风湿性关节炎 （VARA） 登记处的参与者，这些参与者具有经过验证的 ILD 诊断。对参与者进行随访直至死亡或研究期结束。假设常染色体显性遗传，使用 Infinium 基因分型芯片测量 MUC5B rs35705950 启动子变体。生存和死因是根据 VA 死亡记录和国家死亡指数确定的。在 Cox 回归模型中测试了 MUC5B 启动子变体与生存率的关联，该模型调整了潜在的混杂因素。结果 在 263 例 RA-ILD 参与者 （平均年龄 69 岁，95% 男性，73% 白人，85% 吸烟史） 中，MUC5B 启动子变异存在于 33.5% 的比例中。有 （12.2/100PY [95% CI： 9.4， 15.8]） 和无 （11.1/100PY [95% CI： 9.1， 13.5]） 该变异的患者死亡率相似。MUC5B 状态与总生存期 （aHR 0.97 [95% CI： 0.68， 1.37]）或按 ILD 模式分层 （临床常见间质性肺炎 [UIP] aHR 0.86 [95% CI： 0.55， 1.35];临床非 UIP aHR 1.15 [95% CI： 0.63， 2.09] ] 无显著相关性。此外，MUC5B 状态与呼吸相关 （aHR 0.83 [95% CI： 0.42， 1.66]） 或非呼吸系统死亡原因 （aHR 1.08 [95% CI： 0.72， 1.62]） 无显著相关性。结论 虽然与 RA-ILD 风险相关，但 MUC5B 启动子变异不能预测该多中心队列中 RA-ILD 患者的生存率。需要进一步的研究来确定 RA-ILD 中的其他遗传和非遗传预后因素，以便为疾病管理提供信息。