Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, 35128, Padova, Italy.
Respir Res. 2021 Apr 1;22(1):98. doi: 10.1186/s12931-021-01694-z.
A common variant located in the promoter region of MUC5B (rs35705950) is the strongest risk factor for sporadic and familiar IPF, as well as a predictor of outcome. However, there are no data on the effect of MUC5B rs35705950 genotype on the prognosis of IPF patients on antifibrotic treatment. The aim of this study is to determine, in a phenotypically well-characterized population of patients with IPF treated with antifibrotics, the impact of MUC5B rs35705950 genotype on disease progression and survival.
88 IPF patients on antifibrotic treatment were followed-up from 2014 until transplantation, death or end of follow-up (December 2019). Disease progression was defined as a forced vital capacity (FVC) loss ≥ 5% per year. All patients were genotyped for MUC5B rs35705950 by PCR amplification and Sanger sequencing.
Out of 88 patients, 61 (69%) carried the mutant T allele (TT or TG) and 27 (31%) did not (GG). Carriage of the MUC5B rs35705950 T allele was not associated with a faster decline in FVC. Conversely, at the end of the follow-up, overall survival in carriers of the TT/TG genotype was longer compared to that of the GG genotype carriers. FVC (L) at baseline and time to respiratory failure at rest were independent predictors of worse prognosis.
In IPF patients on antifibrotic treatment, carriage of the MUC5B rs35705950 T allele is associated with longer survival, highlighting the usefulness of MUC5B genetic data in clinical decision making.
位于 MUC5B（rs35705950）启动子区域的常见变异是散发性和家族性特发性肺纤维化（IPF）的最强风险因素，也是结局的预测因子。然而，关于 MUC5B rs35705950 基因型对接受抗纤维化治疗的 IPF 患者预后的影响尚无数据。本研究的目的是在接受抗纤维化治疗的表型特征良好的 IPF 患者人群中，确定 MUC5B rs35705950 基因型对疾病进展和生存的影响。
对 88 名接受抗纤维化治疗的 IPF 患者进行随访，随访时间从 2014 年至移植、死亡或随访结束（2019 年 12 月）。疾病进展定义为用力肺活量（FVC）每年下降≥5%。所有患者均通过 PCR 扩增和 Sanger 测序进行 MUC5B rs35705950 基因分型。
在 88 例患者中，61 例（69%）携带突变 T 等位基因（TT 或 TG），27 例（31%）不携带（GG）。携带 MUC5B rs35705950 T 等位基因与 FVC 下降速度加快无关。相反，在随访结束时，TT/TG 基因型携带者的总生存率长于 GG 基因型携带者。基线时 FVC（L）和静息时发生呼吸衰竭的时间是预后不良的独立预测因子。
在接受抗纤维化治疗的 IPF 患者中，携带 MUC5B rs35705950 T 等位基因与更长的生存时间相关，这突出了 MUC5B 遗传数据在临床决策中的有用性。
