内脏脂肪组织与骨关节炎因果关联的分析  

Causal relationship between visceral adipose tissue and osteoarthritis

作　　者：孙鹏程 章晓云[2] 黎征鹏 李勇进 高振罡 李坤健 Sun Pengcheng;Zhang Xiaoyun;Li Zhengpeng;Li Yongjin;Gao Zhengang;Li Kunjian(Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China;Ruikang Hospital,Guangxi University of Chinese Medicine,Nanning 530011,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学,广西壮族自治区南宁市530000 [2]广西中医药大学附属瑞康医院,广西壮族自治区南宁市530011

出　　处：《中国组织工程研究》2025年第12期2631-2640,共10页Chinese Journal of Tissue Engineering Research

基　　金：中医药人才队伍建设专项经费-桂派中医大师培养项目(部门预算社[2023]1号),项目参与人:章晓云;广西中医药大学A类“桂派中医药传承创新团队”(2022A004),项目参与人:章晓云。

摘　　要：背景:尽管肥胖与骨关节炎之间存在关联,但作为肥胖关键因素的内脏脂肪组织与骨关节炎之间的因果关系尚不明确。目的:采用两样本孟德尔随机化方法探讨内脏脂肪组织与骨关节炎的因果关系。方法:从大规模全基因组关联分析(GWAS)中筛选出221个与内脏脂肪组织强相关且无连锁不平衡的单核苷酸多态性。骨关节炎的汇总数据来自一项大型全基因组关联分析,纳入了来自9个不同人群多达826690名受试者(177517名骨关节炎患者和649173名对照)。采用两样本孟德尔随机化评估内脏脂肪组织与早期任意部位骨关节炎(45岁之前)、任意部位骨关节炎、膝骨关节炎、髋骨关节炎、膝/髋骨关节炎、脊柱骨关节炎、拇指骨关节炎、手指骨关节炎之间的因果关联。以逆方差加权为主要方法进行孟德尔随机化分析,同时将加权中位数法、MR-Egger法用于补充说明。结果与结论:①逆方差加权分析结果显示,内脏脂肪组织对早期任意部位骨关节炎(OR=1.91,95%CI:1.64-2.24,P=6.04×10^(-16))、任意部位骨关节炎(OR=1.44,95%CI:1.38-1.49,P=3.65×10^(-75))、膝骨关节炎(OR=1.87,95%CI:1.75-2.00,P=1.29×10-79)、髋骨关节炎(OR=1.34,95%CI:1.24-1.45,P=2.84×10^(-14))、膝/髋骨关节炎(OR=1.71,95%CI:1.62-1.80,P=2.97×10^(-83))、脊柱骨关节炎(OR=1.42,95%CI:1.31-1.54,P=8.89×10^(-17))、拇指骨关节炎(OR=1.26,95%CI:1.10-1.44,P=6.21×10^(-4))、手指骨关节炎(OR=1.29,95%CI:1.13-1.49,P=2.68×10^(-4))具有正向因果效应;②敏感性分析结果显示,内脏脂肪组织对8种骨关节炎的因果效应没有异质性、多效性或异常值;③结果提示内脏脂肪组织是骨关节炎的风险因素,过多的内脏脂肪组织可能会增加患骨关节炎的风险。BACKGROUND:Although obesity is associated with osteoarthritis,it remains unclear whether visceral adipose tissue has a causal relationship with osteoarthritis.OBJECTIVE:To investigate the causal relationship between visceral adipose tissue and osteoarthritis using two-sample Mendelian randomization methods.METHODS:A total of 221 single nucleotide polymorphisms strongly associated with visceral adipose tissue without linkage disequilibrium were screened from the genome-wide association study(GWAS).Pooled data for osteoarthritis were derived from a large genome-wide association analysis that included up to 826690 subjects(177517 osteoarthritis patients and 649173 controls)from nine different populations.We conducted two-sample Mendelian randomization analyses to assess the causal associations between visceral adipose tissue and early-onset any-site osteoarthritis(before age 45),any-site osteoarthritis,knee osteoarthritis,hip osteoarthritis,knee or hip osteoarthritis,spinal osteoarthritis,thumb osteoarthritis,and finger osteoarthritis.Inverse variance weighting was employed as the primary Mendelian randomization analysis method,with weighted median and MR-Egger methods used for supplementary clarification.RESULTS AND CONCLUSION:Inverse variance weighting results revealed a positive causal effect of visceral adipose tissue on eight types of osteoarthritis:early-onset any-site osteoarthritis[odds ratio(OR)=1.91,95%confidence interval(CI):1.64-2.24,P=6.04×10^(-16)],any-site osteoarthritis(OR=1.44,95%CI:1.38-1.49,P=3.65×10^(-75)),knee osteoarthritis(OR=1.87,95%CI:1.75-2.00,P=1.29×10^(-79)),hip osteoarthritis(OR=1.34,95%CI:1.24-1.45,P=2.84×10^(-14)),knee or hip osteoarthritis(OR=1.71,95%CI:1.62-1.80,P=2.97×10^(-83)),spinal osteoarthritis(OR=1.42,95%CI:1.31-1.54,P=8.89×10^(-17)),thumb osteoarthritis(OR=1.26,95%CI:1.10-1.44,P=6.21×10^(-4)),and finger osteoarthritis(OR=1.29,95%CI:1.13-1.49,P=2.68×10^(-4)).Sensitivity analyses showed no heterogeneity,pleiotropy,or outliers in the causal effects of visceral adipose ti

关 键 词：内脏脂肪组织 骨关节炎 全基因组关联分析 孟德尔随机化 因果关联 单核苷酸多态性 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R684.3