Objectives The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis (RA)-related interstitial lung disease (ILD), but not with systemic sclerosis (SSc)-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general. Methods We performed a cross-sectional study of SSc-ILD patients from 4 US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and non-UIP groups. Analysis of HRCTs performed by a thoracic radiologist blinded to participants’ characteristics classified each scan as definite UIP, probable UIP, indeterminate, or alternative diagnosis, according to American Thoracic Society criteria. Results Four-hundred eighty-nine SSc-ILD patients were included; 80% were female and 75% were White. Twenty-three (4.7%) patients had a definite UIP pattern. The MUC5B SNP rs35705950 was not associated with a definite UIP pattern in SSc-ILD. In contrast, patients carrying 2 copies of the IPF risk gene FAM13A minor allele rs2609255 had significantly higher odds of a definite UIP pattern compared with the other patterns (OR 3.40, 95% CI 1.19–9.70), and compared with an alternative diagnosis (OR 3.65, 95% CI 1.25–10.65). Conclusion We demonstrated a novel association between FAM13A and SSc-UIP. Contrary to IPF and RA-ILD, the MUC5B promoter polymorphism was not associated with a definite UIP pattern in SSc-ILD.

中文翻译：

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FAM13A 多态性与系统性硬化症相关间质性肺病患者常见的间质性肺炎模式相关


目的 MUC5B 启动子单核苷酸多态性 （SNP） rs35705950 与特发性肺纤维化 （IPF） 和类风湿性关节炎 （RA） 相关间质性肺病 （ILD） 相关，但与系统性硬化症 （SSc）-ILD 无关。我们假设 MUC5B 启动子多态性或其他 IPF 易感基因座与不常见的 SSc 常见间质性肺炎 （UIP） 内表型的风险增加相关，而不是一般的 SSc-ILD。方法 我们对来自 4 个美国硬皮病项目的 SSc-ILD 患者进行了横断面研究，以调查 MUC5B rs35705950 和 12 个其他 IPF 易感基因位点的频率。通过高分辨率胸部 CT （HRCT） 影像学检查结果将 SSc-ILD 患者分为 UIP 组和非 UIP 组。根据美国胸科学会的标准，由不了解参与者特征的胸部放射科医生对 HRCT 进行的分析将每次扫描分为明确的 UIP、可能的 UIP、不确定或其他诊断。结果 共纳入 489 例 SSc-ILD 患者;80% 是女性，75% 是白人。23 例 （4.7%） 患者有明确的 UIP 模式。MUC5B SNP rs35705950 与 SSc-ILD 中的明确 UIP 模式无关。相比之下，与其他模式相比，携带 2 个 IPF 风险基因 FAM13A 次要等位基因 rs2609255 的患者明确 UIP 模式的几率显着更高 （OR 3.40,95% CI 1.19-9.70），与其他诊断相比 （OR 3.65,95% CI 1.25-10.65）。结论 我们证明了 FAM13A 与 SSc-UIP 之间存在新的关联。与 IPF 和 RA-ILD 相反，MUC5B 启动子多态性与 SSc-ILD 中明确的 UIP 模式无关。