摘要
目的采用双样本孟德尔随机化方法分析干燥综合征(SS)与原发性胆汁性胆管炎(PBC)以及肝功能异常的因果关系。方法从全基因组关联研究中提取SS、PBC、碱性磷酸酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转移酶、直接胆红素、总胆红素水平的核苷酸多态性作为工具变量,以逆方差加权(IVW)分析法为主,辅以加权中位数、MR-Egger、加权模型、简单模型分析方法进行补充,并通过一系列敏感性分析验证结果稳健性。结果PBC对SS的IVW分析结果:P=8.57E-11,OR=1.1859,95%CI=1.1264~1.2485;SS对PBC的IVW分析结果,差异无统计学意义。SS对碱性磷酸酶的IVW分析结果:IVW:P=0.0415,Beta=-0.0072,95%CI=-0.0140~-0.0003;SS对丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转移酶、直接胆红素、总胆红素水平的IVW分析结果,差异无统计学意义。结论PBC能显著增加SS患病风险,而不能证实SS对PBC的发生有因果影响。SS有潜在降低碱性磷酸酶水平的作用,而不能证实SS与丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转移酶、直接胆红素、总胆红素水平有因果关系。
Objective To analyze the causal relationship between Sjogren′s syndrome(SS)and primary biliary cholangitis(PBC)and abnormal liver function by two-sample Mendelian randomization.Methods From the genome-wide association study,single nucleotide polymorphisms of SS,PBC,alkaline phosphatase,alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,direct bilirubin and total bilirubin levels were extracted as instrumental variables.Inverse-variance weighted(IVW)analysis was used as the main analysis,supplemented by weighted median,MR-Egger,weighted mode,and simple mode.And a series of sensitivity analyses were carried out to verify the robustness of the results.Results The IVW analysis results of PBC on SS were as follows:P=8.57E-11,OR=1.1859,95%CI=1.1264-1.2485;IVW analysis of PBC on SS(P>0.05).IVW analysis results of SS on alkaline phosphatase were as follows:P=0.0415,Beta=-0.0072,95%CI=-0.0140——0.0003;IVW analysis results of SS on alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,direct bilirubin,total bilirubin levels showed no statistically significant difference.Conclusion PBC can significantly increase the risk of SS,but SS cannot be proved to have a causal effect on the occurrence of PBC.SS has a potential effect on reducing alkaline phosphatase levels,but it is not proved that SS has causal relationship with alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,direct bilirubin,total bilirubin levels.
作者
周莉涵
徐俊
郭晟
李逸雪
徐子皓
程良斌
Zhou Lihan;Xu Jun;Guo Sheng;Li Yixue;Xu Zihao;Cheng Liangbin(Clinical College of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430061;Dept of Hepatology,Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430061)
出处
《安徽医科大学学报》
CAS
北大核心
2024年第10期1856-1862,共7页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金项目(编号:82274367)
湖北省自然科学基金项目(编号:2024AFD328)
全国名老中医药专家传承工作室建设项目(编号:国中医药人教函[2022]75号)。
关键词
孟德尔随机化
因果关系
原发性胆汁性胆管炎
干燥综合征
肝功能异常
Mendelian randomization
causal relationship
primary biliary cholangitis
Sjogren′s syndrome
abnormal liver function
