A SNP altering the MUC5AC mucin structure is increased in idiopathic pulmonary fibrosis together with the MUC5B SNP.

IF 5.7 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2026-07-28 DOI:10.1186/s12931-026-03833-w

Sergio Trillo-Muyo, Anna Ermund, Brendan Dolan, Levent M Akyürek, Jesper M Magnusson, Gunnar C Hansson

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引用次数: 0

Abstract

Background: The gel-forming mucins MUC5B and MUC5AC constitute the main structural components of mucus in the respiratory system where MUC5AC is known to form nets. The MUC5B (rs35705950) Single Nucleotide Polymorphism (SNP) has been shown to increase the risk for Idiopathic Pulmonary Fibrosis (IPF). The MUC5AC SNP rs878913005, common in European populations, results in an Arg1201Trp substitution, resulting in more stabilized secreted mucin nets. Here we investigate the association of rs878913005 with the development of IPF and the presence of the two mucins in IPF diagnostic honeycomb cysts.

Methods: We compared patient groups using whole genome sequences from the UK-Biobank for the SNPs in MUC5AC and MUC5B mucin genes. Lung tissue from IPF patients were immunostained for these mucins.

Results: The MUC5AC SNP shows a significant 1.49x increased frequency in IPF patients relative to controls (p < 0.0001) and an odds ratio of 2.09. The well-known IPF-associated SNP in the MUC5B promoter (rs35705950) has a stronger linkage to IPF when combined with the MUC5AC SNP. These two SNPs are located on the same chromosome and are in linkage disequilibrium (r² = 0.10 in controls and up to r² = 0.17 in IPF). Microscopic honeycomb cysts, typical for IPF, are filled with both the MUC5B and MUC5AC mucins with MUC5AC associated to the cysts' epithelial surface.

Conclusion: A genetic variant with more stable MUC5AC nets in peripheral thin airways may increase the risk of IPF.

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改变MUC5AC粘蛋白结构的SNP与MUC5B SNP一起在特发性肺纤维化中增加。

背景：形成凝胶的粘蛋白MUC5B和MUC5AC构成了呼吸系统粘液的主要结构成分，其中MUC5AC形成网状。MUC5B （rs35705950）单核苷酸多态性（SNP）已被证明可增加特发性肺纤维化（IPF）的风险。MUC5AC SNP rs878913005在欧洲人群中很常见，导致Arg1201Trp取代，导致分泌的粘蛋白网更稳定。本研究探讨了rs878913005与IPF发展的关系，以及这两种粘蛋白在IPF诊断蜂窝囊肿中的存在。方法：我们使用UK-Biobank的全基因组序列比较患者组MUC5AC和MUC5B粘蛋白基因的snp。对IPF患者的肺组织进行了这些粘蛋白的免疫染色。结果：MUC5AC SNP在IPF患者中的频率比对照组显著增加1.49倍（对照组p 2 = 0.10， IPF组最高r2 = 0.17）。显微镜下蜂窝囊肿是典型的IPF，充满MUC5B和MUC5AC粘蛋白，MUC5AC与囊肿上皮表面相关。结论：外周薄气道MUC5AC网络更稳定的基因变异可能增加IPF的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.