C反应蛋白与心脏传导障碍两样本孟德尔随机化研究

C-reactive protein and cardiac conduction disorders: a two-sample Mendelian randomization study

目的 探讨C反应蛋白(CRP)与心脏传导障碍的因果关联。方法 使用两样本孟德尔随机化分析方法,选择与血清CRP浓度相关的单核苷酸多态性(SNP)作为工具变量,在204 402例欧洲血统个体的全基因组关联研究中进行分析。利用FinnGen数据库(第2版)的汇总数据,分别获得与3种心脏传导障碍[房室传导阻滞(AV-block)、左束支传导阻滞(LBBB)、右束支传导阻滞(RBBB)]相关的遗传变异。采用逆方差加权法进行主分析,然后分别应用敏感性分析、多效性检验和留一法评估结果的可靠性。结果 共50个SNPs纳入为工具变量。逆方差加权分析显示,遗传预测的血清CRP浓度与心脏传导障碍之间无明显因果关联,结果分别为AV-block(比值比0.983,95%可信区间0.820~1.177,P=0.849)、LBBB(比值比1.201,95%可信区间0.911~1.583,P=0.194)、RBBB(比值比1.292,95%可信区间0.881~1.894,P=0.194)。敏感性分析结果显示,CRP与AV-block、LBBB和RBBB均无显著相关性(P>0.05)。多效性检验显示,CRP与AV-block、LBBB和RBBB均不存在异质性和多效性(P>0.05)。留一法提示,移除单个SNP对结果无显著影响。结论 血清CRP浓度与心脏传导障碍不存在因果关联。

Objective To investigate the causal relationship between C-reactive protein(CRP)and cardiac conduction disorders.Methods Single nucleotide polymorphism(SNP)associated with serum CRP concentration were selected as instrumental variables in a genome-wide association study of 204 402 individuals of European ancestry using two-sample mendelian randomization analysis.Genetic variants associated with three heart conduction disorders[atrioventricular block(AV-block),left bundle branch block(LBBB),and right bundle branch block]were obtained using pooled data from the FinnGen database(2nd edition).The inverse variance weighting method was used for the main analysis, and then sensitivity analysis, pleiotropy test and remain-one method were used respectively to evaluate the reliability of the results.Results A total of 50 SNPs were included as instrumental variables.Inverse variance weighted analysis showed no significant causal association between genetically predicted serum CRP concentration and cardiac conduction disorders, and the results were AV-block(odds ratio 0.983,95% confidence interval 0.820 to 1.177,P=0.849),LBBB(odds ratio 1.201,95% confidence interval 0.911 to 1.583,P=0.194)and RBBB(odds ratio 1.292,95% confidence interval 0.881 to 1.894,P=0.194).Sensitivity analysis showed that CRP was not significantly correlated with atrioventricular block, left bundle branch block and right bundle branch block(P>0.05).Pleiotropy test showed no heterogeneity or pleiotropy between CRP and AV-block, BBB,BB(P>0.05).The remain-one method suggests that removing a single SNP has no significant effect on the results.Conclusion There is no causal relationship between CRP concentration and cardiac conduction disorder.