1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland.
Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland.
Int J Mol Sci. 2023 Jun 28;24(13):10748. doi: 10.3390/ijms241310748.
Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.
特发性肺纤维化（IPF）是一种与暴露相关的间质性肺疾病，具有两种表型 - 纤维化和非纤维化。遗传易感性是疾病发病机制和纤维化发展的重要因素。有几个基因被认为与肺部的纤维化级联反应有关。其中最受认可和最常见的是常见的 MUC5B 基因启动子区域多态性变异 rs35705950。我们研究的目的是确定 HP 患者人群中 MUC5B 基因的次要等位基因的频率，并发现 MUC5B 启动子区域多态性与肺纤维化的发展、疾病过程的严重程度以及 HP 患者对治疗的反应之间的关系。对 86 例连续的 HP 患者进行了 MUC-5B 基因 rs35705950 遗传变异的检测。收集了人口统计学、影像学和功能参数。分析了 T 等位基因的存在与肺纤维化、肺功能测试参数以及治疗反应之间的关系。研究组的次要等位基因频率为 17%，其中基因型 GG 分布在 69.8%的受试者中，GT/TT 分布在 30.2%的受试者中。GT/TT 表型的患者基础用力肺活量（FVC）显著降低，且随时间推移 FVC 下降的频率显著更高。与 GG 携带者相比，高分辨率计算机断层扫描（HRCT）中肺纤维化的患病率在 GT/TT 变体携带者中没有显著增加。携带 T 等位基因的患者对免疫调节治疗的反应较差，更频繁地接受抗纤维化药物治疗。结论：HP 患者 MUC5B 多态性的频率较高。T 等位基因可能预示着疾病过程更差、免疫调节治疗反应更差以及更早需要抗纤维化治疗。
