辛伐他汀预防胆石症的孟德尔随机化研究  

Mendelian randomization of simvastatin in preventing cholelithiasis

作　　者：牛斌[1] 佘林璐 翁康强 李沪 吴翔 戴英波 Bin Niu;Linlu She;Kangqiang Weng;Hu Li;Xiang Wu;Yingbo Dai(Department of Gastrointestinal Surgery,the Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,China;Department of Urology,the Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,China)

机构地区：[1]中山大学附属第五医院胃肠外科,珠海519000 [2]中山大学附属第五医院泌尿外科,珠海519000

出　　处：《中华肝脏外科手术学电子杂志》2025年第1期60-67,共8页Chinese Journal of Hepatic Surgery(Electronic Edition)

摘　　要：目的利用全基因组关联(GWAS)分析相关数据,通过孟德尔随机化(MR)研究探讨辛伐他汀对胆石症的预防作用。方法采用MR研究方法,以基因工具变量探讨辛伐他汀预防胆石症的作用。以ieuopen GWAS数据库公开发表的基因数据为参考依据,借助R语言平台,筛选出与辛伐他汀关联有统计学意义的单核甘酸多态性(SNP)作为工具变量,通过逆方差加权分析法(IVW)、加权中位数法(WM)和MR-Egger法分别判断辛伐他汀与胆石症的因果关联,绘制SNP相关的辛伐他汀与胆石症风险的森林图及散点图。结果共筛选出36个与辛伐他汀相关的SNP。IVW分析(OR=0.956,95%CI:0.935~0.978,P=8.57×10^(-5))、WM分析(OR=0.957,95%CI:0.926~0.983,P=1.82×10^(-3))、MR-Egger回归法分析(OR=0.963,95%CI:0.922~1.007,P=1.07×10^(-1))均显示辛伐他汀与胆石症具有负相关因果关联。MR-Egger回归法分析表明无多效性(截距=-6.36×10^(-5),P=0.69)。根据散点图直线斜率判断,IVW、WM、MR-Egger回归法分析的因果关联估计相近。辛伐他汀每增加一个标准差,胆石症的发病风险减低约4.4%。结论两样本MR分析结果表明,辛伐他汀与胆石症的发病风险存在负向因果关系,辛伐他汀每增加一个标准差,胆石症发病风险会降低约4.4%。Objective To analyze related data by genome-wide association studies(GWAS)and evaluate preventive effect of simvastatin on cholelithiasis by Mendelian randomization(MR).Methods MR was adopted to evaluate the preventive effect of simvastatin on cholelithiasis with genetic variants as instrumental variables.Based on the published gene data in ieuopen GWAS database,the single nucleotide polymorphism(SNP)with significant association with simvastatin was selected as an instrumental variable using R language platform.The causal association between simvastatin and cholelithiasis was evaluated by inverse-variance weighted(IVW),weighted median(WM)and MR-Egger methods,respectively.The forest and scatter plots of simvastatin and the risk of cholelithiasis associated with SNP were delineated.Results A total of 36 SNPs associated with simvastatin were screened.IVW(OR=0.956,95%CI:0.935-0.978,P=8.57×10^(-5)),WM(OR=0.957,95%CI:0.926-0.983,P=1.82×10^(-3))and MR-Egger regression analyses(OR=0.963,95%CI:0.922-1.007,P=1.07×10^(-1))showed negative causal association between simvastatin and cholelithiasis.MR-Egger regression analysis indicated no pleiotropic effect(intercept=-6.36×10^(-5),P=0.69).According to the slope of the straight line in the scatter plot,the causal correlation estimates were similar among IVW,WM and MR-Egger regression methods.With every one standard deviation(SD)increase of simvastatin,the risk of cholelithiasis decreased by approximately 4.4%.Conclusions MR analysis of two samples demonstrates that there is a negative causal association between simvastatin and the risk of cholelithiasis.The risk of cholelithiasis will decreased by approximately 4.4% with every one SD increase of simvastatin.

关 键 词：辛伐他汀 胆结石 孟德尔随机化 胆固醇饱和指数 

分 类 号：R657.42[医药卫生—外科学]