The 2nd Clinical Medical College of Jinan University, Shenzhen, 518000, China.
Lujiazui Community Health Service Center, Pudong New Area, shanghai, China.
Sci Rep. 2024 Oct 10;14(1):23698. doi: 10.1038/s41598-024-74455-9.
Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005-3.262, P = 0.048). Although IL-12β and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention.
先前的研究表明，高身体质量指数（BMI）可能是圆锥角膜（KC）的一个风险因素，但因果关系尚不清楚。本研究采用孟德尔随机化（MR）来研究这种关联，并探讨循环血清代谢物和炎症因子在这种关联中的中介作用。进行了两样本 MR 分析，以评估 BMI 与 KC 之间的关系。该研究采用两步 MR 方法来评估 91 种炎症标志物和 249 种血清代谢物在 BMI-KC 关系中的中介作用。逆方差加权（IVW）是主要方法，并进行了多种敏感性分析以确保稳健性。IVW 分析显示 BMI 和 KC 之间存在正相关的因果关系（OR IVW=1.811，95%CI 1.005-3.262，P=0.048）。尽管 IL-12β和 IL-4 与 KC 有因果关系，但它们并未介导 BMI-KC 关系。确定了 5 种血清代谢物作为潜在的中介物，其中高密度脂蛋白胆固醇和甘油三酯比值具有显著意义。本研究阐明了高 BMI 与 KC 之间的因果关系，表明高 BMI 可能通过脂质代谢异常诱导 KC。这些发现强调了管理 BMI 以预防 KC 的重要性。
