α-klotho reduces susceptibility to osteoarthritis: evidence from cross-sectional studies and Mendelian randomization

Despite extensive research, the association between serum α-klotho levels and osteoarthritis (OA) remains unclear, predominantly relying on findings from OA mouse models. This study used data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional study examin...

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Veröffentlicht in:Frontiers in endocrinology (Lausanne) Jg. 15; S. 1450472
Hauptverfasser: Li, Zhao, Li, Zhong, Cheng, Qisheng, Nie, Xinlin, Cui, Yu, Du, Bing, Ren, Taotao, Xu, Yibo, Ma, Teng
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 19.11.2024
Schlagworte:
Adult
Aged
causal effect
Cohort Studies
Cross-Sectional Studies
Disease Susceptibility
Endocrinology
Female
Genetic Predisposition to Disease
Glucuronidase - blood
Glucuronidase - genetics
Humans
Klotho Proteins
Male
Mendelian randomization
Mendelian Randomization Analysis
Middle Aged
NHANES
Nutrition Surveys
osteoarthritis
Osteoarthritis - blood
Osteoarthritis - genetics
Osteoarthritis - metabolism
α-klotho
α-klotho
NHANES
causal effect
Mendelian randomization
osteoarthritis
ISSN:1664-2392, 1664-2392
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Zusammenfassung:Despite extensive research, the association between serum α-klotho levels and osteoarthritis (OA) remains unclear, predominantly relying on findings from OA mouse models. This study used data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional study examining the relationship between α-klotho and human OA. In addition, we used Mendelian randomization (MR) to genetically infer a causal relationship between serum α-klotho and the three OA subtypes. A cohort of 12,037 subjects from NHANES (2007-2016) was analyzed. Multivariate logistic regression was utilized to examine the association between α-klotho concentration and OA, alongside subgroup analysis and interaction tests. Additionally, a two-sample bi-directional MR analysis was conducted to evaluate the relationship between serum α-klotho and three OA subtypes, including all OA, hip OA, and knee OA, employing the inverse variance weighting (IVW) method as the primary approach. Following adjustment for covariates, a nonlinear negative correlation between serum α-klotho and OA was observed (OR=0.77; 95% CI, 0.68-0.88, p < 0.0001). The IVW method revealed that higher serum α-klotho levels were associated with decreased susceptibility to hip OA (OR = 0.92, 95% CI: 0.87-0.98, P = 9.64×10 ). However, MR analysis did not establish a causal relationship between serum α-klotho and OA or knee OA. Inverse MR also indicated that the three subtypes of OA do not causally affect serum α-klotho concentrations. In cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies.
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Reviewed by: Assunta Pozzuoli, University of Padua, Italy
Edited by: Rita Cassia Menegati Dornelles, São Paulo State University, Brazil
These authors have contributed equally to this work
Yang Sun, The University of Auckland, New Zealand
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2024.1450472