| Title: | α-klotho reduces susceptibility to osteoarthritis: evidence from cross-sectional studies and Mendelian randomization |
| Journal: | Frontiers in Endocrinology |
| Published: | 19 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39629050/ |
| DOI: | https://doi.org/10.3389/fendo.2024.1450472 |
Publication 14096
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Abstract
Background: 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.</p>
Method: 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.</p>
Results: 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 = 9.64×10-3). 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.</p>
Conclusions: In cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies.</p>
15 Keywords
- Adult
- Aged
- Cohort Studies
- Cross-Sectional Studies
- Disease Susceptibility
- Female
- Genetic Predisposition to Disease
- Glucuronidase
- Humans
- Klotho Proteins
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Nutrition Surveys
- Osteoarthritis
9 Authors
- Zhao Li
- Zhong Li
- Qisheng Cheng
- Xinlin Nie
- Yu Cui
- Bing Du
- Taotao Ren
- Yibo Xu
- Teng Ma
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