基于孟德尔随机化的4种脂质成分与痛风的因果关联研究  

Causal association between 4 kinds of lipid ingredients and gout:a Mendelian randomization study

作　　者：刘思园 陈欣熠 徐英英[2] LIU Siyuan;CHEN Xinyi;XU Yingying(Third Clinical Medical College,Zhejiang University of Chinese Medicine,Hangzhou,Zhejiang 310053,China;Department of Endocrinology,Third Affiliated Hospital of Zhejiang University of Chinese Medicine,Hangzhou,Zhejiang 310005,China)

机构地区：[1]浙江中医药大学第三临床医学院,杭州310053 [2]浙江中医药大学附属第三医院内分泌科,杭州310005

出　　处：《重庆医学》2024年第17期2619-2624,2630,共7页Chongqing Medical Journal

基　　金：浙江省中山医院医药卫生计划项目(ZS21ZA03)。

摘　　要：目的采用两样本孟德尔随机化(MR)分析方法探究4种脂质成分[甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)]与痛风的因果关联。方法利用大样本全基因关联研究汇总数据,选择与4种脂质成分密切相关的遗传位点作为工具变量,以逆方差加权(IVW)法为主,加权中位数(WME)、MR-Egger回归法、简单模式法和加权模式法为辅对数据进行两样本MR分析。以比值比(OR)值评价4种脂质成分与痛风间的因果关系,异质性检验、基因多效性检验和敏感性分析3种方法评估结果的稳定性和可靠性。结果高甘油三酯血症可增加痛风的患病风险(OR=1.85,95%CI:1.29~2.66,P<0.01),而TC(OR=1.12,95%CI:0.78~1.62,P=0.553)、HDL-C(OR=0.76,95%CI:0.52~1.11,P=0.156)、LDL-C(OR=1.25,95%CI:0.95~1.63,P=0.105)与痛风患病风险的因果关联不明显。IVW和MR-Egger回归的异质性检验结果表明不存在异质性,MR-Egger回归法截距项检验结果显示不存在基因多效性,Leave-one-out分析未发现非特异性单核苷酸多态性(SNP)位点。结论TG升高与痛风间可能存在正向因果关联,提示高甘油三酯血症人群应积极检测并注意预防痛风发生。Objective To investigate the causal association between four kinds of lipid components[total cholesterol(TC),triglyceride(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(HDL-C)]and gout by using the two-sample Mendelian randomization analysis method.Methods The pooled data with a large sample of whole gene association studies were utilized to study the summarized data.The genetic loci closely related to four lipid components were selected as the instrumental variables.The inverse variance weighting method(IVW)was used as the main method,and weighted median(WME),MR-Egger regression,simple model method and weighted model method as the supplement,the data conducted the two samples MR analysis.The causal association among 4 kinds of lipid components with gout was evaluated by odds ratios(OR)value.The three methods of heterogeneity tests,pleiotropy tests and sensitivity analysis were used to assess the stability and reliability of the results.Results Hypertriglyceridemia could increase the risk of developing gout(OR=1.85,95%CI:1.29-2.66,P<0.01).However TC(OR=1.12,95%CI:0.78-1.62,P=0.553),HDL-C(OR=0.76,95%CI:0.52-1.11,P=0.156)and LDL-C(OR=1.25,95%CI:0.95-1.63,P=0.105)had no significant causal association with the risk of developing gout.The heterogeneity test results of IVW method and MR-Egger regression showed that there was no heterogeneity and the MR-Egger regression intercept test showed no pleiotropy.The test result of MR-Egger regression intercept term method showed that there was no gene pleiotropy.The Leave-one-out analysis did not find the non-specific single nucleotide polymorphisms(SNP)locus.Conclusion There may be a positive causal association between elevated TC and gout,suggesting that the population with hypertriglyceridemia should actively detect and pay attention to prevent the onset of gout.

关 键 词：甘油三酯 总胆固醇 低密度脂蛋白胆固醇 高密度脂蛋白胆固醇 痛风 孟德尔随机化 

分 类 号：R589[医药卫生—内分泌]