孟德尔随机化法探究TGF-β与AAMI后左室舒张末容积的关系  

Investigation the relationship between TGF-βlevel and left ventricular volume after AAMI based mendelian randomization

作　　者：刘泽岩[1] 周姝[1] 张浩[1] 程景林[1] LIU Zeyan;ZHOU Shu;ZHANG Hao;CHENG Jinglin(Emergency Internal Medicine Department,the Second Affiliated Hospital of Anhui Medical University,Hefei 230000,China)

机构地区：[1]安徽医科大学第二附属医院急诊内科,安徽合肥230000

出　　处：《安徽医学》2023年第5期523-527,共5页Anhui Medical Journal

基　　金：安徽医科大学校基金青年项目(编号:2021xkj286)。

摘　　要：目的采用孟德尔随机化方法(MR)探究转化生长因子-β(TGF-β)水平与急性前壁心肌梗死(AAMI)急性期后左室舒张末容积(LVEDV)的因果关系。方法从基因组和表观基因组关联研究(GWAS/EWAS)数据库选取TGF-β和AAMI后LVEDV数据。TGF-β数据包括982例样本,LVEDV数据包括35 407例样本。选择与TGF-β独立相关的显著基因位点作为工具变量,分别使用逆方差加权法(IVW)、加权中位数、加权模式法及MR-Egger回归研究TGF-β与AAMI急性期后LVEDV的关系。结果逆方差加权法(IVW)法结果显示,TGF-β升高能增加AAMI后LVEDV扩大的风险(OR=1.021,95%CI:1.007~1.035,P=0.004)。与加权中位数法(OR=1.017,95%CI:1.008~1.026,P=2.26×10~(-4))及加权模式法(OR=1.014,95%CI:1.000~1.028,P=0.043),结果一致。MR-Egger回归截距为-0.002(95%CI:-0.018~0.014,P=0.791),表明工具变量几乎不存在多效性。散点图及漏斗图均提示,研究结果稳定可靠。结论TGF-β水平与AAMI急性期后LVEDV存在正向因果效应,即TGF-β升高能导致AAMI急性期后LVEDV扩大。Objective To investigate the causal relationship between transforming growth factor-β(TGF-β)level and left ventricular end-diastolic volume(LVEDV)after acute anterior myocardial infarction(AAMI)by Mendelian randomization(MR).Methods TGF-βand LVEDV data were selected from genome and epigenome association study(GWAS/EWAS)database.TGF-βdata included 982 samples and LVEDV data included 35407 samples.Significant loci independently associated with TGF-βwere selected as instrumental variables,and MR analysis was performed using inverse variance weighted,weighted median,weighed mode and MR-Egger regression respectively.Results The inverse variance weighting(IVW)method showed that TGF-βincreased risk of LVEDV expansion after AAMI(OR=1.021,95%CI:1.007-1.035,P=0.004).The conclusion of different methods was consistent:weighted median method(OR=1.017,95%CI:1.008-1.026,P=2.26×10-4);weighted mode method(OR=1.014,95%CI:1.000-1.028,P=0.043).The intercept of MR-Egger regression was-0.002(95%CI:-0.018-0.014,P=0.791),indicating that there was almost no pleiotropy in instrumental variables.Both scatter plot and funnel plot suggested that the re-sults were stable and reliable.Conclusions There is a positive causal effect between TGF-βlevel and LVEDV after acute phase of AAMI,that is,the increase of TGF-βcan lead to the expansion of LVEDV after acute phase of AAMI.

关 键 词：孟德尔随机化 转化生长因子-Β 心肌梗死 左室舒张末容积 

分 类 号：R542.22[医药卫生—心血管疾病]