Objectives Rheumatoid arthritis (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% confidence interval [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. Conclusions 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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罕见单核苷酸变异MUC5B rs35705950与日本类风湿性关节炎间质性肺疾病的关联


目的 类风湿性关节炎（RA）有时会并发间质性肺病（ILD），预后较差。 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 患者中没有发现这种 SNV 的关联，因为它在日本人群中的频率非常低。我们研究了候选 SNV（包括 MUC5B 变体）与日本 RA 中 ILD 的关联。方法对日本 RA 患者的 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 与普通间质性肺炎 (UIP)（p = 0.0039，Pc = 0.0156，比值比 [OR] 10.66，95% 置信区间 [CI] 2.05-55.37）或 ILD（p = 0.0071，Pc = 0.0284，在等位基因模型下，日本 RA 中的 OR 7.33，95%CI 1.52-35.44）。 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 与日本 RA 中的 UIP 存在主要关联。未观察到 MAD1L1 rs12699415 或 PPFIBP2 rs6578890 与 RA 中的 UIP、非特异性间质性肺炎或 ILD 存在显着关联。结论 MUC5B rs35705950 与日本 RA 中 ILD，尤其是 UIP 的发病相关，并可能参与其中。