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

蔡奔; 刘婷; 高洁; 肖莉萍; 施恒远; 丁言稳; 贾贤杰; 于影

doi:10.13898/j.cnki.issn.1000-2200.2021.06.027

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

摘要

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β_{IVW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β_IVW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。

Abstract:
ObjectiveTo explore the causal relationship between alcohol consumption and post-stroke cognitive impairment(PSCI) based on Mendelian.
MethodsBased 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.
ResultsThe 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 was β_{IVW alcohol consumption history}=0.606(OR=3.334, 95%CI: 3.038-3.653), and the causality between PSCI and blush after alcohol consumption was β_{IVW blush after drinking}=0.320(OR=4.908, 95%CI: 4.739-6.475).
ConclusionsThere is a positive causality between PSCI, and history of alcohol consumption and blush after drinking in patients with ischemic stroke before admission.

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