% 0期刊文章% Aabida Saferali %一个丹迪巧% Wonji金正日%凯伦Raraigh %征收Hara % Alejandro A·迪亚兹%加里·r·切%迈克尔·h·曹%克雷格·p·赫什%,% TC 功能处理量变异与慢性支气管炎的吸烟者2022% % D J R 10.1183/13993003.01994 -2021%欧洲呼吸杂志% P 2101994 % V 60% N 2% X引入功能丧失变体在囊性纤维化跨膜电导调节的两个副本(雌性生殖道)基因导致囊性纤维化(CF);然而,有证据表明,减少雌性生殖道功能由于存在一个有害的变异可以有临床后果。在这里,我们假设在雌性生殖道变异个体的吸烟与慢性阻塞性肺疾病(COPD)和相关的表型。执行全基因组测序方法通过国家心脏、肺、血液研究所TOPMed (TransOmics精密医学)计划在8597年从COPDGene (COPD)的遗传流行病学研究,现任和前任吸烟者的观察研究。我们提取临床带注释的雌性生殖道变体进行了单独的变种和慢性阻塞性肺病variant-set测试相关的表型。复制了2118年主题从ECLIPSE(评价慢性阻塞性肺病纵向识别预测替代终点)的研究。结果我们发现301个编码变异基因在雌性生殖道内边界:147年在CF患者已报告,包括36 CF-causing变体。我们发现CF-causing变异与慢性支气管炎在COPDGene variant-set测试(单边p = 0.0025;或1.53)和荟萃分析COPDGene和ECLIPSE(单边p = 0.0060;或1.52)。 Single-variant testing revealed that the F508del variant was associated with chronic bronchitis in COPDGene (one-sided p=0.015; OR 1.47). In addition, we identified 32 subjects with two or more CFTR variants on separate alleles and these subjects were enriched for COPD cases (p=0.010).Conclusions Cigarette smokers who carry one deleterious CFTR variant have higher rates of chronic bronchitis, while presence of two CFTR variants may be associated with COPD. These results indicate that genetically mediated reduction in CFTR function contributes to COPD related phenotypes, in particular chronic bronchitis.Cigarette smokers who carry one deleterious CFTR variant have higher rates of chronic bronchitis, while presence of two CFTR variants associates with COPD. These results indicate that genetically mediated reduction in CFTR function contributes to COPD. https://bit.ly/3GSWUXw %U //www.qdcxjkg.com/content/erj/60/2/2101994.full.pdf