基于孟德尔随机化分析的饮酒与缺血性脑卒中PSCI因果关联研究  

Causal association between alcohol consumption and post-stroke cognitive impairment based on Mendelian randomization study

作　　者：蔡奔 刘婷 高洁[2] 肖莉萍 施恒远 丁言稳 贾贤杰[1] 于影[2] CAI Ben;LIU Ting;GAO Jie;XIAO Li-ping;SHI Heng-yuan;DING Yan-wen;JIA Xian-jie;YU Ying(Department of Epidemiology and Health Statistics,Bengbu Medical College,Bengbu Anhui 233030,China;Department of Physiology,Bengbu Medical College,Bengbu Anhui 233030,China)

机构地区：[1]蚌埠医学院流行病与卫生统计学教研室,安徽蚌埠233030 [2]蚌埠医学院生理学教研室,安徽蚌埠233030

出　　处：《蚌埠医学院学报》2021年第6期817-821,共5页Journal of Bengbu Medical College

基　　金：安徽省高校自然科学研究重点项目(KJ2017A217;KJ2019A0306);蚌埠医学院转化医学重点专项(BYTM2019004);“512人才培育计划”(by51201202/by51201307);蚌埠医学院研究生科研创新计划(Byycx1904)。

摘　　要：目的:采用孟德尔随机化分析方法探讨饮酒与缺血性脑卒中认知功能障碍(post-stroke cognitive impairment,PSCI)之间因果关联。方法:基于孟德尔随机化逆方差加权法(inverse-variance weighted,IVW),利用工具变量如酒精代谢强相关基因ALDH2不同基因型评估饮酒相关暴露因素和PSCI的因果关系,采用二分类logistic分析方法检验相关显著性。结果:文化程度、饮酒后是否脸红和是否有饮酒史对病人PSCI的影响具有统计学意义(P<0.05)。从病人全血中提取DNA浓度为(54.88±20.59)ng/μL,纯度均在1.7~1.9之间,通过ALDH2 rs671位点的多态性决定其基因型,其中G突变为A,野生GG型76例,突变杂合AG型52例和突变纯和AA型3例,该基因位点经过Hardy-Weinberg遗传平衡定量分析显示具有恒定性(P>0.05)。有饮酒史与PSCI之间的因果关系值为βIVW有饮酒史=0.606(OR=3.334,95%CI:3.038~3.653),饮酒后脸红与PSCI之间的因果关系值为βIVW脸红=0.320(OR=4.908,95%CI:4.739~6.475)。结论:缺血性脑卒中病人入院前有饮酒史和饮酒后脸红与其PSCI存在正向因果关联。Objective:To explore the causal relationship between alcohol consumption and post-stroke cognitive impairment(PSCI)based on Mendelian.Methods:Based on Mendelian randomization inverse-variance weighted(IVW),the causal relationship between drinking-related exposure factors and PSCI was evaluated using instrumental variables such as ALDH2 genotypes,and two-classification logistics analysis was used to test the significance of correlation.Results:The differences of the effects of the education level,flush after drinking and history of alcohol consumption on PSCI were statistically significant(P<0.05).The concentration and purity of DNA in whole blood of patients were(54.88±20.59)ng/μL and(1.7-1.9),respectively.The genotype was determined by the polymorphism of ALDH2 rs671 site,and the G mutated to A.There were 76 cases of wild GG type,52 cases of mutant heterozygous AG type and 3 cases of mutant pure and AA type,the results of quantitative analysis of Hardy-Weinberg genetic balance showed that this gene locus was stable(P>0.05).The causality between PSCI and history of alcohol consumption wasβIVW alcohol consumption history=0.606(OR=3.334,95%CI:3.038-3.653),and the causality between PSCI and blush after alcohol consumption wasβIVW blush after drinking=0.320(OR=4.908,95%CI:4.739-6.475).Conclusions:There is a positive causality between PSCI,and history of alcohol consumption and blush after drinking in patients with ischemic stroke before admission.

关 键 词：缺血性脑卒中 饮酒 认知功能障碍 孟德尔随机化研究 

分 类 号：R743.3[医药卫生—神经病学与精神病学]