罕见单核苷酸变异MUC5B rs35705950与日本类风湿关节炎患者间质性肺疾病的关联

Association of rare single nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis.

作者信息

Higuchi Takashi, Oka Shomi, Shimada Kota, Tsunoda Shinichiro, Ito Satoshi, Okamoto Akira, Fujimori Misuzu, Nakamura Tadashi, Katayama Masao, Suzuki Michita, Saisho Koichiro, Shinohara Satoshi, Matsui Toshihiro, Migita Kiyoshi, Nagaoka Shouhei, Tohma Shigeto, Furukawa Hiroshi

机构信息

Department of Rheumatology, NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan.

Clinical Research Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 252-0392, Japan.

出版信息

Rheumatology (Oxford). 2024 Aug 7. doi: 10.1093/rheumatology/keae422.

DOI:10.1093/rheumatology/keae422

PMID:39110542

Abstract

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.

摘要

目的

类风湿关节炎（RA）有时会并发间质性肺疾病（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患者中未发现该SNV的相关性，因为其在日本人群中的频率非常低。我们研究了包括MUC5B变异在内的候选SNV与日本RA患者ILD的相关性。

方法

对日本RA患者进行MUC5B rs35705950、MUC2 rs7934606、MAD1L1 rs12699415和PPFIBP2 rs6578890的基因分型以进行关联分析。

结果

在等位基因模型下，MUC5B rs35705950与日本RA患者的寻常型间质性肺炎（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，OR 7.33，95%CI 1.52 - 35.44）相关。MUC2 rs7934606与RA患者的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患者的UIP主要相关。未观察到MAD1L1 rs12699415或PPFIBP2 rs6578890与RA患者的UIP、非特异性间质性肺炎或ILD有显著相关性。