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Updated: May 16, 2025

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Genetically determined α-Klotho levels and causal association with aging-related lung diseases
Chen Jin1, Ruiying Jin1, Dingyu Liu1
1Key Laboratory of Aging and Cancer Biology of Zhejiang Province, School of Basic Medical Sciences, Hangzhou Normal University and School of Public Health, Hangzhou Normal University, Hangzhou, 311121, China.
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, PIVW-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.
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