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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Vydané v:	Frontiers in endocrinology (Lausanne) Ročník 15; s. 1450472
Hlavní autori:	Li, Zhao, Li, Zhong, Cheng, Qisheng, Nie, Xinlin, Cui, Yu, Du, Bing, Ren, Taotao, Xu, Yibo, Ma, Teng
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland Frontiers Media S.A 19.11.2024
Predmet:	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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Abstract	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.
AbstractList	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. BackgroundDespite 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.MethodA 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.ResultsFollowing 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.ConclusionsIn cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies. 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.BackgroundDespite 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.MethodA 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 = 9.64×10-3). 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.ResultsFollowing 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.In cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies.ConclusionsIn cross-sectional studies, α-klotho showed a nonlinear negative correlation with OA. MR analysis of outcomes was not identical to cross-sectional studies.
Author	Ren, Taotao Cui, Yu Ma, Teng Cheng, Qisheng Du, Bing Li, Zhao Li, Zhong Nie, Xinlin Xu, Yibo
AuthorAffiliation	2 Department of Orthopedic Center, The First Hospital of Jilin University , Changchun , China 1 Honghui Hospital, Xi’an Jiaotong University , Xi’an , China
AuthorAffiliation_xml	– name: 1 Honghui Hospital, Xi’an Jiaotong University , Xi’an , China – name: 2 Department of Orthopedic Center, The First Hospital of Jilin University , Changchun , China
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Cites_doi	10.1093/hmg/ddab263 10.1002/acr.v62:11 10.3390/biomedicines10061369 10.1038/s41398-023-02632-x 10.1016/j.bbrc.2010.06.110 10.1007/s13238-019-00685-7 10.1016/j.bone.2012.02.012 10.1002/art.34420 10.1177/0962280215597579 10.1038/s41467-022-35359-2 10.1136/annrheumdis-2019-216515 10.1016/j.mcna.2019.10.007 10.1016/j.joca.2009.11.012 10.1136/annrheumdis-2013-203355 10.1038/s41467-019-14156-4 10.1016/j.joca.2011.07.015 10.1016/j.jbiomech.2021.110931 10.18632/aging.102603 10.1016/S0140-6736(12)60681-3 10.3389/fendo.2023.1251167 10.1038/s43587-021-00051-5 10.1210/er.2013-1079 10.1002/gepi.2013.37.issue-7 10.1007/s00424-009-0722-7 10.1016/j.joca.2006.12.002 10.1038/s41588-018-0327-1 10.1002/art.23176 10.1016/j.jot.2015.02.002 10.1038/36285 10.1155/2011/203901 10.1016/j.joca.2021.11.009 10.1126/science.1112766 10.18632/aging.101481 10.1016/j.mad.2018.12.003 10.1016/S0140-6736(14)60802-3 10.1016/j.coph.2013.01.010 10.1016/j.rceng.2024.04.012 10.1016/j.bone.2012.02.002 10.3389/fendo.2020.00560 10.1001/jama.2021.18236
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Keywords	α-klotho NHANES causal effect Mendelian randomization osteoarthritis
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Snippet	Despite extensive research, the association between serum α-klotho levels and osteoarthritis (OA) remains unclear, predominantly relying on findings from OA... BackgroundDespite extensive research, the association between serum α-klotho levels and osteoarthritis (OA) remains unclear, predominantly relying on findings...
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StartPage	1450472
SubjectTerms	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
Title	α-klotho reduces susceptibility to osteoarthritis: evidence from cross-sectional studies and Mendelian randomization
URI	https://www.ncbi.nlm.nih.gov/pubmed/39629050 https://www.proquest.com/docview/3140929662 https://pubmed.ncbi.nlm.nih.gov/PMC11611571 https://doaj.org/article/35f7d8a6235b4e06aa022fb42d4cac3a
Volume	15
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