Abstract
Klotho, a protein primarily expressed in the kidneys and brain, plays a critical role in aging, vascular health, and various metabolic processes. Lower serum Klotho levels have been associated with several chronic diseases, including cardiovascular disease, diabetes, and kidney disease. Although the role of Klotho in platelet regulation remains underexplored, thrombocytosis may be influenced by Klotho levels. Investigating this relationship could offer new insights into thrombocytosis pathogenesis. This study aimed to examine the relationship between serum Klotho levels and thrombocytosis in a U.S. cohort. We hypothesized that lower Klotho levels would be associated with an increased risk of thrombocytosis, potentially providing a novel perspective on thrombocytosis regulation. We conducted a cross-sectional analysis of data from 12,700 participants in the NHANES 2007-2016 cohort. Multivariate logistic regression models were used to assess the association between serum Klotho levels and thrombocytosis, adjusting for relevant covariates. Of the 12,700 participants, 86 had thrombocytosis. The thrombocytosis group had significantly lower mean serum Klotho levels compared to the non-thrombocytosis group (p < 0.01). After adjusting for confounders, an inverse association between serum Klotho levels and thrombocytosis was observed (odds ratio 0.89, 95% CI 0.82-0.97, p = 0.007). Compared to the lowest Klotho quartile (≤ 700.7 pg/ml), the adjusted odds ratios for thrombocytosis in the second (700.8-915.3 pg/ml) and third (≥ 915.4 pg/ml) quartiles were 0.6 (95% CI: 0.36-1.01, p = 0.055) and 0.49 (95% CI: 0.29-0.84, p = 0.01), respectively. Our findings suggest an inverse correlation between serum Klotho levels and thrombocytosis in adults aged 40 and older. These results highlight the potential role of Klotho in thrombocytosis regulation, and future longitudinal studies are needed to establish causality and explore the underlying mechanisms.