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肺间质异常与端粒平均长度缩短有关。

Interstitial lung abnormalities are associated with decreased mean telomere length.

机构信息

Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

出版信息

Eur Respir J. 2022 Aug 25;60(2). doi: 10.1183/13993003.01814-2021. Print 2022 Aug.

Abstract

BACKGROUND

Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL).

METHODS

Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality.

RESULTS

In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively).

CONCLUSION

ILA are associated with decreased MTL.

摘要

背景

间质性肺异常(ILA)与特发性肺纤维化有许多共同特征;然而,ILA 是否与平均端粒长度(MTL)降低有关尚不清楚。

方法

在慢性阻塞性肺疾病(COPDGene)和年龄基因/环境易感性雷克雅未克(AGES-Reykjavik)队列中,通过定量 PCR 测量端粒长度,在弗雷明汉心脏研究(FHS)中使用Southern 印迹分析。使用逻辑和线性回归评估 ILA 与 MTL 之间的关联;使用 Cox 比例风险模型评估 MTL 与死亡率之间的关联。

结果

在所有三个队列中,ILA 与 MTL 降低有关。在 COPDGene 和 AGES-Reykjavik 队列中,在调整后,与最长四分位数相比,端粒长度最短四分位数的 ILA 发生几率增加了两倍以上(比值比 2.2,95%置信区间 1.5-3.4,p=0.0001,和 OR 2.6,95%CI 1.4-4.9,p=0.003)。在 FHS 中,有 ILA 的人的端粒比没有 ILA 的人短(-767bp,95%CI 76-1584bp,p=0.03)。尽管在 COPDGene 中,MTL 降低与慢性阻塞性肺疾病相关(比值比 1.3,95%置信区间 1.1-1.6,p=0.01),但与 ILA 相比,其效应估计值较小。在 COPDGene 和 AGES-Reykjavik 中,比较端粒最短四分位数时,MTL 与死亡风险之间没有一致的关联(HR 0.82,95%CI 0.4-1.7,p=0.6,和 HR 1.2,95%CI 0.6-2.2,p=0.5)。

结论

ILA 与 MTL 降低有关。

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