Genetically Determined α-Klotho Levels and Causal Association with Aging-Related Lung Diseases.

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, Yuwen Li

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引用次数: 0

Abstract

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.