Objectives RA is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single-nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA. Methods Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415 and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses. Results MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (P = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% CI 2.05–55.37) or ILD (P = 0.0071, Pc = 0.0284, OR 7.33, 95% CI 1.52–35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (P = 0.0072, Pc = 0.0288, OR 29.55, 95% CI 1.52–574.57) or ILD (P = 0.0037, Pc = 0.0148, OR 22.95, 95% CI 1.27–416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed. Conclusion MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA.

中文翻译：

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罕见的单核苷酸变异 MUC5B rs35705950 与日本类风湿关节炎间质性肺病的相关性


目的 RA 有时并发间质性肺病 （ILD） 且预后不良。MUC5B 中的单核苷酸变异 （SNV） 与欧洲 RA 患者的 ILD 相关。然而，在日本 RA 患者中未发现这种 SNV 的关联，因为它在日本人群中的发生率非常低。我们研究了候选 SNV 的关联，包括 MUC5B 变体与日本 RA 中的 ILD。方法 对日本 RA 患者 MUC5B rs35705950 、 MUC2 rs7934606 、 MAD1L1 rs12699415 和 PPFIBP2 rs6578890 进行基因分型进行关联分析。结果 MUC5B rs35705950 与日本 RA 的普通间质性肺炎 （UIP） （P = 0.0039，Pc = 0.0156，比值比 [OR] 10.66,95% CI 2.05-55.37）或 ILD （P = 0.0071，Pc = 0.0284，OR 7.33,95% CI 1.52-35.44） 在等位基因模型下日本 RA 相关。MUC2 rs7934606 与 RA 中的 UIP （P = 0.0072，Pc = 0.0288，OR 29.55,95% CI 1.52–574.57） 或 ILD （P = 0.0037，Pc = 0.0148，OR 22.95,95% CI 1.27–416.13） 相关。单倍型分析表明 MUC5B rs35705950 与 UIP 在日本 RA 中的主要关联。在 RA 中未观察到 MAD1L1 rs12699415 或 PPFIBP2 rs6578890 与 UIP 、非特异性间质性肺炎或 ILD 的显著关联。结论 MUC5B rs35705950 与日本 RA 中 ILD 尤其是 UIP 的发病机制相关，并可能参与其发病机制。