Inverse association between serum Klotho levels and rheumatoid arthritis risk: Insights from the NHANES database

Abstract Background Klotho is a type I transmembrane protein known for its anti‐aging, anti‐inflammatory, antioxidative, and cognitive‐enhancing properties. It also exhibits protective effects against systemic lupus erythematosus, sclerosis, and other diseases. The aim of this study was to investigate the relationship between serum Klotho levels and the risk of rheumatoid arthritis (RA). Methods Participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016 were included. Data on RA prevalence, serum Klotho levels, and other covariates were analyzed. Weighted Mann−Whitney U tests, χ 2 tests, and univariate and multivariate logistic regression analyses were performed to explore the association between serum Klotho levels and RA risk. Results Serum Klotho levels were significantly lower in the RA group compared to the control group ( p = 0.028). Univariate weighted logistic regression analysis revealed that participants in the highest Klotho quartile had a significantly lower risk of RA than those in the lowest quartile (OR = 0.80, p = 0.010). This association remained significant in multivariate weighted logistic regression models (Model 1: OR = 0.83, p = 0.040; Model 2: OR = 0.81, p = 0.020). Conclusions Serum Klotho levels are negatively correlated with RA risk. Maintaining normal serum Klotho levels may be crucial in preventing the onset and progression of RA. Longitudinal and mechanistic studies are necessary to better account for confounding factors and to elucidate the mechanisms underlying the protective role of serum Klotho in RA.