基因决定的α-Klotho水平与衰老相关肺部疾病的因果关系

IF 3.5 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Respiratory medicine Pub Date : 2025-04-01 DOI:10.1016/j.rmed.2025.108081

Chen Jin, Ruiying Jin, Dingyu Liu, Yuwen Li

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引用次数: 0

摘要

背景：α-Klotho （KL）水平异常在衰老相关肺部疾病的发病机制中起重要作用。然而，循环KL水平与衰老相关肺部疾病之间的相关性尚未确定。本研究旨在利用孟德尔随机化（MR）确定循环KL水平是否与衰老相关的肺部疾病有因果关系。方法：采用双样本MR分析了5个kl相关的单核苷酸多态性（snp），以评估它们对三种与衰老相关的肺部疾病：特发性肺纤维化（IPF）、慢性阻塞性肺疾病（COPD）和肺癌的影响。结果：采用逆方差加权（IVW）方法，包括乘性随机效应模型（IVW-mre）和固定效应逆方差加权模型（IVW-fe）进行MR分析，遗传预测循环KL水平与IPF风险呈负相关(优势比（oriw -mre）， 0.999, 95% CI, 0.999 ~ 1.000, piw -mre = 0.008；OR IVW-fe, 0.999, 95% CI, 0.999-1.000, piw -fe = 0.042)。相反，KL的循环水平与COPD和肺癌没有明显的关联。未发现多效性。结论：遗传预测的循环KL与IPF风险降低有因果关系，提示在预防IPF风险方面具有保护作用。因此，KL可能是IPF患者预防和治疗干预的一个有希望的靶点。

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Genetically determined α-Klotho levels and causal association with aging-related lung diseases

Background

Abnormal α-Klotho (KL) levels play an essential role in the pathogenesis of aging-related lung diseases. However, the correlation between circulating KL levels and aging-related lung diseases has not been determined. This study aimed to determine whether circulating KL levels causally affect aging-related lung diseases using Mendelian randomization (MR).

Methods

Five KL-associated Single-nucleotide polymorphisms (SNPs) were analyzed using two-sample MR to assess their effects on three aging-related lung diseases: idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and lung cancer.

Results

Based on a main casual effects model with MR analyses by the inverse variance weighted (IVW) method including multiplicative random-effects model (IVW-mre) and fixed-effects inverse variance-weighted model (IVW-fe), genetically predicted circulating KL levels were negatively related with risk of IPF (Odds ratio (OR_IVW-mre), 0.999, 95 % CI, 0.999–1.000, P _IVW-mre = 0.008; OR _IVW-fe, 0.999, 95 % CI, 0.999–1.000, P_IVW-fe = 0.042). Inversely, the circulating levels of KL displayed no clear association with COPD and lung cancer. No pleiotropy was detected.

Conclusions

Genetically predicted circulating KL was causally associated with a lower risk of IPF, suggesting a protective effect in preventing IPF risk. Therefore, KL may be a promising target for the prevention and therapeutic intervention in patients with IPF.

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来源期刊

Respiratory medicine 医学-呼吸系统

CiteScore

7.50

自引率

0.00%

发文量

199

审稿时长

38 days

期刊介绍： Respiratory Medicine is an internationally-renowned journal devoted to the rapid publication of clinically-relevant respiratory medicine research. It combines cutting-edge original research with state-of-the-art reviews dealing with all aspects of respiratory diseases and therapeutic interventions. Topics include adult and paediatric medicine, epidemiology, immunology and cell biology, physiology, occupational disorders, and the role of allergens and pollutants. Respiratory Medicine is increasingly the journal of choice for publication of phased trial work, commenting on effectiveness, dosage and methods of action.