Rheumatology (Oxford, England) · 2025
Association of rare single-nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.