循环炎症蛋白与心肌肥厚:来自GWAS Catalog与芬兰数据库欧洲群体的大样本分析  

Circulating inflammatory proteins and myocardial hypertrophy:large sample analysis of European populations from GWAS Catalog and FinnGen databases

作　　者：丁宇 陈婧雯 陈秀燕 施慧敏 杨雨蝶 周美启 崔帅[1,3] Ding Yu;Chen Jingwen;Chen Xiuyan;Shi Huimin;Yang Yudie;Zhou Meiqi;Cui Shuai(College of Acupuncture and Massage,Anhui University of Chinese Medicine,Hefei 230001,Anhui Province,China;First Affiliated Hospital of Nanjing Medical University,Nanjing 210000,Jiangsu Province,China;Anhui Provincial Key Laboratory of Meridian-Organ Correlation,Hefei 230001,Anhui Province,China)

机构地区：[1]安徽中医药大学针灸推拿学院,安徽省合肥市230001 [2]南京医科大学第一附属医院,江苏省南京市210000 [3]经脉脏腑相关安徽省重点实验室,安徽省合肥市230001

出　　处：《中国组织工程研究》2026年第4期1047-1057,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家重点研发计划课题(2022YFC3500502),项目负责人:周美启;优秀青年教师培育重点项目(YQZD2023046),项目负责人:崔帅。

摘　　要：背景:心肌肥厚常会导致严重的心血管疾病,由于早期难以被发现,因此很难确诊。循环炎症蛋白被发现与心血管疾病有相当大的关联,但其与心肌肥厚关系的具体机制依然不明确。目的:采用多种孟德尔随机化的方法探究循环炎症蛋白和心肌肥厚间的关系。方法:采用GWAS Catalog数据库中的91个循环炎症蛋白数据库和最新版R11芬兰数据库中的心肌肥厚数据,利用双向两样本孟德尔随机化、多变量孟德尔随机化和全基因组关联研究共定位分析的方式探寻循环炎症蛋白和心肌肥厚的因果关系。用MR-PRESSO方法、Cochran’sQ检验、MR-Egger截距评估、留一法分析和漏斗图分析等敏感性检验的方式验证结果的准确性。结果与结论:(1)在双向两样本孟德尔随机化结果中主要用逆方差加权法(Inverse Variance Weighting,IVW)进行评估,发现T细胞表面糖蛋白CD6异构体水平(IVW:P=0.046,OR=0.74,95%CI:0.66-1.00),裂隙趋化因子水平(IVW:P=2.1×10^(-2),OR=0.74,95%CI:0.556-0.95),Delta和Notch样表皮生长因子相关受体水平(IVW:P=3.7×10^(-4),OR=0.66,95%CI:0.49-0.87),白细胞介素2水平(IVW:P=3.8×10^(-3),OR=0.667,95%CI:0.50-0.88),硫酸转移酶1A1(IVW:P=1.42×10^(-2),OR=0.80,95%CI:0.67-0.96)对心肌肥厚具有单向因果作用。(2)在多变量孟德尔随机化中发现,T细胞表面糖蛋白CD6异构体水平(IVW:P=1.39×10^(-2),OR=0.81,95%CI:0.69-0.96)和Delta和Notch样表皮生长因子相关受体水平(IVW:P=3.7×10^(-2),OR=0.73,95%CI:0.55-0.98)的结果为阳性,说明排除了其他和心肌肥厚具有影响的循环炎症蛋白影响后其结果依然显著。(3)在共定位中发现,T细胞表面糖蛋白CD6异构体水平H3+H4=0.96,其中最显著的单核苷酸多态性为rs59570070,说明T细胞表面糖蛋白CD6异构体水平和心肌肥厚存在内在联系。(4)敏感性结果无异常,说明无异质性和多效性影响结果。(5)结果证实,T细胞表面糖蛋白CD6异构体、裂隙趋化因BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran’s Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95%CI:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95%CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95%CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×10-3,OR=0.667,95%CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×10-2,OR=0.80,95%CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×10-2,OR=0.81,95%CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95%CI:0.55-0.98)were positive,indicatin

关 键 词：心肌肥厚 循环炎症蛋白 心血管疾病 孟德尔随机化 因果关系 观察性研究 共定位 多变量孟德尔随机化 

分 类 号：R452[医药卫生—治疗学] R318[医药卫生—临床医学] R542.2