脂肪酸种类及含量与膝骨关节炎的发病风险  

Types and contents of fatty acids and the risk of knee osteoarthritis

作　　者：汤熙然 陈伟坚 姜涛 谭羡允 刘文刚 Tang Xiran;Chen Weijian;Jiang Tao;Tan Xianyun;Liu Wengang(Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Guangdong Second Traditional Chinese Medicine Hospital(Guangdong Institute of Traditional Chinese Medicine Engineering Technology),Guangzhou 510095,Guangdong Province,China)

机构地区：[1]广州中医药大学,广东省广州市510405 [2]广东省第二中医院(广东省中医药工程技术研究院),广东省广州市510095

出　　处：《中国组织工程研究》2025年第17期3724-3731,共8页Chinese Journal of Tissue Engineering Research

基　　金：广东省基础与应用基础研究基金—自然科学基金项目面上项目(2023A1515012615),项目负责人:刘文刚;广东省基础与应用基础研究基金—省企联合基金—面上项目(2022A1515220157),项目负责人:刘文刚;广东省第二中医院科研创新基金—卓越团队项目(SEZYY2023B16),项目负责人:刘文刚。

摘　　要：背景:近年来,流行病学研究显示肥胖是膝骨关节炎的危险因素,而脂肪酸的摄入、代谢和生物合成与肥胖的发生发展密切相关,但脂肪酸与膝骨关节炎之间是否存在因果关联仍未知。目的:应用孟德尔随机化分析方法探讨5种脂肪酸表型与膝骨关节炎的因果关联。方法:使用来自英国生物银行(met-D)的脂肪酸比例的全基因组关联研究数据和来自EBI-A数据库的膝骨关节炎的全基因组关联研究数据进行汇总,将单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量并选择敏感的SNPs进行分析,通过双样本孟德尔随机化分析,以评估脂肪酸与膝骨关节炎结局风险的因果关系。采用逆方差加权法、MR-Egger回归法、加权中位数法、加权模型法和简单模型法来研究脂肪酸与膝骨关节炎之间的因果关系。进一步以同样方法进行反向孟德尔随机化分析,确保结果的有效性。结果与结论:①正向分析逆方差加权法结果表明,共有3种脂肪酸表型与膝骨关节炎有因果关系,其中饱和脂肪酸占总脂肪酸的比例(OR=1.825,95%CI:1.230-2.706,P=0.003)与膝骨关节炎的发病风险呈正相关、Ω3多不饱和脂肪酸占总脂肪酸的比例(OR=0.822,95%CI:0.689-0.981,P=0.03)与膝骨关节炎的发病风险呈负相关以及Ω6多不饱和脂肪酸占总脂肪酸的比例(OR=1.268,95%CI:1.079-1.491,P=0.004)与膝骨关节炎的发病风险呈正相关;有2种脂肪酸表型与膝骨关节炎不具有因果关系,为总脂肪酸(OR=0.925,95%CI:0.804-1.066,P=0.283)、单不饱和脂肪酸占总脂肪酸的比例(OR=0.877,95%CI:0.756-1.018,P=0.084)。②反向分析结果表明,当膝骨关节炎作为暴露数据时,与脂肪酸的表型均不具有显著因果关系。③敏感性分析结果显示:双向孟德尔随机化的Cochran’s Q检验和MR-Egger回归法的结果P值均大于0.05,表明脂肪酸表型与膝骨关节炎之间的因果效应分析不存在显著的异质性和多BACKGROUND:In recent years,epidemiological studies have shown that obesity is a risk factor for knee osteoarthritis,and fatty acid intake,metabolism and biosynthesis are closely related to the development of obesity.However,the causal relationship between fatty acids and osteoarthritis is still unknown.OBJECTIVE:Using the Mendelian randomization analysis to investigate the causal relationship between five fatty acid phenotypes and knee osteoarthritis.METHODS:The genome-wide association study data on fatty acid ratios from the UK Biobank(met-D)and genome-wide association study data on knee osteoarthritis from the EBI-A database were pooled together.Single nucleotide polymorphisms were used as instrumental variables and sensitive single nucleotide polymorphisms were selected for analysis.Two-sample Mendelian randomization analysis was conducted to evaluate the causal relationship between fatty acids and knee osteoarthritis outcome risk.We used inverse variance weighting method,MR-Egger regression method,weighted median method,weighted model method,and simple model method to study the causal relationship between fatty acids and knee osteoarthritis.Further inverse Mendelian randomization analysis was performed in the same way to ensure the validity of the results.RESULTS AND CONCLUSION:The forward analysis and inverse variance weighting method showed a causal relationship between three types of fatty acid phenotypes and knee osteoarthritis.Among them,the proportion of saturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(odds ratio[OR]=1.825,95%confidence interval(CI):1.230,2.706,P=0.003),the proportion of omega 3 polyunsaturated fatty acids to total fatty acids was negatively correlated with the risk of knee osteoarthritis(OR=0.822,95%CI:0.6888,0.981,P=0.03),and the proportion of omega 6 polyunsaturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis(OR=1.268,95%CI:1.079,1.491,P=0.004).There were two types of fatty ac

关 键 词：膝骨关节炎 孟德尔随机化 因果关系 敏感性分析 逆方差加权法 饱和脂肪酸 多不饱和脂肪酸 促炎细胞因子 脂质代谢 膝关节内收力矩 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R684.3