代谢综合征组成部分与膝关节骨性关节炎的因果关系:孟德尔随机化研究

Association of metabolic syndrome components with knee osteoarthritis:a Mendelian randomization study

目的采用孟德尔随机化分析方法,探讨代谢综合征组成部分与膝关节骨性关节炎的因果关联。方法对全基因关联研究数据库(GWAS)进行数据挖掘,暴露因素为代谢综合征组成部分(腰围水平、甘油三酯水平、高密度脂蛋白胆固醇水平、高血压和2型糖尿病),结局因素为膝关节骨性关节炎。采用逆方差加权法(IVW)、MR-Egger法、Simple Mode法、加权中位数法和Weighted Mode法等回归模型进行孟德尔随机化分析。结果IVW结果显示,腰围水平与膝关节骨性关节炎呈正性相关关系[OR=3.088,95%CI(2.574,3.704),P<0.01];高密度脂蛋白胆固醇水平与膝关节骨性关节炎呈负性相关关系[OR=0.877,95%CI(0.779,0.989),P<0.05]。但IVW未显示甘油三酯水平、高血压和2型糖尿病与膝关节骨性关节炎有因果关系(P>0.05)。ME-Egger截距测试结果不存在多效性(P>0.05),表明孟德尔随机化在本研究中为因果推断的有效方法。结论中心性肥胖及低高密度脂蛋白胆固醇血症是膝关节骨性关节炎的独立危险因素,但甘油三酯水平、高血压和2型糖尿病与膝关节骨性关节炎的因果关系尚不确定。

Objective To investigate the causal association between metabolic syndrome(MetS)components and osteoarthritis of the knee(KOA)by using Mendelian randomization analysis.Methods The genome-wide association study database(GWAS)was mined,in which the exposure factors were MetS components,namely waist circumference(WC)level,triglyceride(TG)level,high-density lipoprotein cholesterol(HDL-C)level,hypertension(HBP),and type 2 diabetes(T2DM),and the outcome factor was KOA.Mendelian randomization analysis was performed using regression models of inverse-variance weighted(IVW),MR-Egger,Simple Mode,Weighted Median,and Weighted Mode methods.Results IVW showed a causal relationship between WC level and KOA with a positive correlation(OR=3.088,95%CI 2.574 to 3.704,P<0.01),and HDL-C level had a causal relationship with KOA with a negative correlation(OR=0.877,95%CI 0.779 to 0.989,P<0.05).IVW did not show a causal relationship between TG levels,HBP,and T2DM with KOA(P>0.05).The results of the ME-Egger intercept test were not multiplicative(P>0.05),indicating that Mendelian randomization was a valid method for causal inference in this study.Conclusion Central obesity and low HDL-C disorder are independent risk factors for KOA.The causal relationship between TG level,HBP,and T2DM with KOA is still uncertain.