Genetically determined α-Klotho levels and causal association with aging-related lung diseases - 24/04/25
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 (ORIVW-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, PIVW-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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | The circulating levels of α-Klotho is causally associated with a lower risk of Idiopathic pulmonary fibrosis (IPF). |
• | The circulating levels of α-Klothoshow no causal effect on chronic obstructive pulmonary disease (COPD)or lung cancer. |
• | α-Klotho is a promising target for the prevention and therapeutic intervention in patients with IPF. |
Keywords : α-Klotho (KL), Aging-related lung diseases, Idiopathic pulmonary fibrosis, Chronic obstructive pulmonary disease, Lung cancer, Mendelian randomization
Plan
Vol 241
Article 108081- mai 2025 Retour au numéro
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