| Research Background:The "Global status report on alcohol and health 2018"released by WHO shows that in 2016,about 600,000 people worldwide died of alcohol-related digestive system diseases,and 400,000 people died of alcohol-related cancers.The liver is the main site of alcohol metabolism and the most important target organ for alcohol-related diseases,but the mechanism of alcohol-induced liver disease is still unclear.Progress of ALD has large individual differences,in addition to differences in drinking methods,genetic factors also affect the occurrence and development of alcoholic liver disease.In recent years,a large number of domestic and foreign studies have revealed that genes related to alcohol metabolism and lipid metabolism may affect the occurrence and development of ALD,providing genetic guidance for screening ALD-susceptible populations and early intervention of diseases.The ALDH2 gene polymorphism causes a great difference in the activity of acetaldehyde dehydrogenase.Its low activity mutations cause acetaldehyde accumulating in the body,which is the reason of alcoholism symptoms.People with low activity mutation gene often show stronger adverse reactions after drinking.This feature reduces the chance of alcohol exposure in such people and indirectly protects drinkers,and ultimately changes the development process of ALD.CYP2E1,as an alcohol oxidative dehydrogenase,has been confirmed to be induced by alcohol in long-term alcoholics(enzyme expression and/or enzyme activity increased).CYP2E1 produces a large amount of reactive oxygen species while metabolizing alcohol,which aggravates the oxidative stress damage of liver cells,thereby affecting the ALD process.Whether the genetic phenotypes of these two alcohol-metabolizing enzymes affect the occurrence and development of ALD,and whether it is related to unhealthy drinking behavior,there is still a lack of relevant research.Different genetic backgrounds can affect the drinking behavior of individual and the liver tolerance to alcohol,which affect disease progression.To explore the relationship between ALDH2,CYP2E1 gene SNP locus,drinking behavior characteristics and the occurrence and development of ALD,which is important for alcohol abstinence guidance and early intervention of ALD.In this study,the process of ALD patients from the beginning of drinking to the diagnosis of Alcoholic cirrhosis was regarded as a whole and their drinking characteristics were described in behavioral science,combined with genetic polymorphisms and drinking characteristics firstly.Exploring the occurrence and development of the disease will provide a theoretical basis for more in-depth research on drinking behavior and its influencing factors,clinical guidance on alcohol withdrawal and early intervention of ALD in the future.Research purposes:(1)Investigate the drinking habits and drinking characteristics of alcoholic males in Shandong,summarize the relationship between drinking behavior,drinking history characteristics and the occurrence and development of AC.Based on drinking characteristics explore the indicators for predicting alcoholic cirrhosis,and the indicators efficacy is tested.(2)Explore the relationship between the rs671 polymorphism of ALDH2 gene SNP locus,the drinking characteristics of alcoholics and the prevalence of AC.(3)Explore the relationship between the rs2515641 polymorphism at the SNP locus of CYP2E1 gene,the drinking characteristics of alcoholics and the prevalence of AC.(4)Use Mendelian randomization method to explore whether there is a causal relationship between drinking characteristics and the onset of AC.Method:Collect information of patients who attended Qilu Hospital from June 2019 to March 2021 and meet the criteria of inclusion and discharge.Questionnaire surveys and medical history inquiry methods were used to collect the drinking characteristics of patients,and the time-drinking volume curve was drawn.Early morning fasting peripheral venous blood was collected for genomic DNA extraction,and the genetic resequencing method was used to detect the SNP polymorphisms of ALDH2 and CYP2E1 genes.Groups and statistical analysis were performed according to the test results and whether they had AC.The measurement data conforming to the normal distribution were compared with independent sample t-test and one-way analysis of variance,the count data was compared with the χ2 test.The non-parametric Kruskal-Wallis test was used to compare the differences between groups for measurement data that did not conform to the normal distribution.Alcohol Accumulation Index predicts alcoholic liver cirrhosis and uses receiver operating characteristic curve to analyze the AAI cut-off value.Multivariate Logistic regression and Mendelian randomization were used to explore the association between drinking behavior and SNP polymorphisms of ALDH2,CYP2E1 genes and the prevalence of AC.Results:Low addiction age,short addiction period and long alcoholism period are risk factors for AC.Alcohol accumulation index can better predict AC.Mendelian randomization analysis indicated that the rs671 and rs2515641 polymorphisms of ALDH2 and CYP2E1 gene SNP polymorphisms can affect the risk of AC by affecting drinking behavior.rs671 polymorphism mainly affects the risk of AC by affecting the alcohol threshold during alcoholism.Carrying the rare allele A of rs671 can reduce the risk of AC.rs2515641 mainly affects the risk of AC by affecting the length of the alcoholism period.Carrying the rare allele T of rs2515641 can reduce the risk of AC.Conclusion:Low addiction age,short addiction period and long alcoholism period are risk factors for AC.Alcohol accumulation index can better predict AC.The rs671 polymorphism of the ALDH2 gene SNP locus can affect the occurrence of AC by affecting the alcohol threshold of patients during alcoholism.Carrying the rare allele A of rs671 can reduce the risk of AC.The SNP locus rs2515641 polymorphism of CYP2E1 gene affects the occurrence of AC by affecting the length of the alcoholism period.Carrying the rare allele T of rs2515641 can reduce the risk of AC. |
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