孟德尔随机化分析HP-IgG水平与胆囊结石的因果关系及临床验证OA
Mendelian randomization analysis of the causal relationship between anti-Helicobacter pylori IgG levels and cholelithiasis and its clinical verification
目的 通过孟德尔随机化(MR)分析抗幽门螺杆菌(Helicobacter pylori,HP)抗体IgG(HP-IgG)水平与胆囊结石之间的因果关系,并通过临床资料分析HP现症感染与胆囊结石的相关性.方法 从全基因组关联研究(GWAS)数据库中筛选与HP-IgG水平及胆囊结石显著相关(P<1×10-5)的单核苷酸多态性(SNP),以HP-IgG水平作为暴露因素,胆囊结石作为结局变量.设置r2<0.001,kb>10 000,排除连锁不平衡;选择F>10的SNPs作为工具变量(IVs).采用逆方差加权(IVW)、MR-Egger回归、加权中位数(WM)、简单模式(simple mode)和加权模式(weighted mode)进行MR分析.Cochran's Q检验IVs的异质性;MR-Egger截距分析和MR-多效性残差和异常值检验(MR-PRESSO)检测IVs的多效性;留一法(leave-one-out)验证分析结果的稳定性.回顾性收集2024年3月至2025年3月期间哈尔滨市第一医院进行13C呼气试验和肝胆彩超检查的1 537例受试者临床资料,分析HP感染与胆囊结石的关联性.结果 IVW结果表明HP-IgG水平与胆囊结石之间不存在因果关系(OR=1.029,95%CI 0.995‒1.065,P=0.094).MR-Egger回归、WM、simple mode和weighted mode的分析结果与IVW结果一致(均P>0.05).Cochran's Q检验结果显示IVs不存在异质性.MR-Egger截距结果显示IVs无多效性.MR-PRESSO检测结果未发现明显离群的SNPs(P=0.913).leave-one-out结果显示本研究结果稳定.临床资料分析表明,HP感染组中胆囊结石的发生率(75/636,11.79%)和非HP感染组中胆囊结石的发生率(128/901,14.21%)差异无统计学意义(χ2=1.895,P>0.05).结论 本研究通过MR分析表明,HP-IgG水平与胆囊结石之间不存在因果关系;临床资料分析显示HP现症感染与胆囊结石之间没有关联性.
Objective To explore the causal relationship between Helicobacter pylori(HP)antibody IgG(HP-IgG)level and cholelithiasis by Mendelian randomization(MR)analysis and its clinical verification.Methods Single nucleotide polymorphism(SNP)which significantly associated with HP-IgG level and cholelithiasis(P<1×10-5)were selected from the Genome-Wide Association Study(GWAS)database,with HP-IgG level as the exposure factor and cholelithiasis as the outcome variable.Linkage disequilibrium parameters were set with r2<0.001 and kb>10 000.SNPs with F>10 were selected as instrumental variables(IVs).MR analysis was conducted by inverse variance weighted(IVW),MR-Egger regression,weighted median,simple mode,and weighted mode.Cochran's Q test was used to assess the heterogeneity of IVs,while MR-Egger intercept and MR-PRESSO were used to evaluate pleiotropy of IVs.The stability of results was confirmed by the leave-one-out method.The clinical data from 1 537 subjects who underwent both 13C breath test and hepatobiliary color Doppler ultrasound examination at Harbin the First Hospital from March 2024 to March 2025 were retrospectively collected,and the association between HP infection and cholelithiasis was further analyzed.Results The IVW result(OR=1.029,95%CI 0.995 to 1.065,P=0.094)showed that there was no causal relationship between HP-IgG level and cholelithiasis.Results from the MR-Egger regression,weighted median,simple mode,and weighted mode similarly demonstrated no correlation(all P>0.05).The Cochran's Q test indicated no heterogeneity in IVs.The MR-Egger intercept analysis confirmed no pleiotropy in IVs.MR-PRESSO analysis revealed no significant outliers in the SNP data(P=0.913).The leave-one-out method confirmed the stability of results.Analysis of the clinical data showed no statistically significant difference(χ2=1.895,P>0.05)in the prevalence of cholelithiasis between the HP-infected group(75/636,11.79%)and the non-HP-infected group(128/901,14.21%).Conclusion This MR analysis demonstrates no causal relationship between HP-IgG level and cholelithiasis.Clinical data analysis indicates no association between current HP infection and cholelithiasis.
胡彦建
哈尔滨市第一医院消化科,黑龙江 哈尔滨 150010
医药卫生
幽门螺杆菌抗幽门螺杆菌抗体IgG胆囊结石孟德尔随机化因果关系临床验证
Helicobacter pylorianti-Helicobacter pylori IgG levelcholelithiasisMendelian randomizationcausal relationshipclinical verification
《肝胆胰外科杂志》 2026 (4)
277-283,7
评论