Association Between Arg47His Mutation In ADH2 Gene And Chronic Hepatitis Disease

BackgroundChronic hepatitis B disease can do great harm to human health and quality of life and affect people's life expectancy.It is also an important cause of death and burden of disease in China and many other countries.So to further the study on the pathogenesis of chronic hepatitis B is very important for the prevention and control of the disease.Chronic hepatitis B disease is the most common cause of chronic hepatitis,and alcohol is one of the major risks to it.Chronic hepatitis B is a multi-factorial disease, which is related to both the genetic and environmental factors.Gene has an important role in chronic hepatitis B incidence.There are research papers that indicate geneenvironment interaction makes great contribution to the risk of chronic hepatitis B.With the advance of Human Genome Project and application of molecular biologic technics,it has become more and more popular in medical fields to clarify the pathogenesis of chronic hepatitis B at gene level.There is much research that indicates a close association between alcohol's damage to liver and chronic hepatitis.Arg47His Mutation in alcohol dehydrogenase (ADH)2 Gene is an important factor that affects alcohol metabolism.So the association between Arg47His Mutation in ADH2 Gene and chronic hepatitis needs be explored further.There is some research that mutation has much to do with alcohol dependence,liver Cirrhosis and liver cancer.However,reports are extremely rare presently on the association between Arg47His Mutation in ADH2 Gene and chronic hepatitis and the interaction between the mutation and other risk factors on chronic hepatitis B.Objective1.To explore the association between Arg47His Mutation in ADH2 Gene and chronic hepatitis B.2.To explore and assess the interaction effect between Arg47His Mutation in ADH2 Gene and other risk factors on chronic hepatitis B and the dose-effect relationship of the interaction.MethodsA hospital-based case-control study was conducted.A total of 252 diagnosed chronic hepatitis B patients in Jinan Infectious Disease hospital and 223 health adults were recruited as study subjects.A PCR-RFLP was performed to detect Arg47His Mutation in ADH2 Gene.Univariate test and multiple logistic regression models were used to analyze the association between Arg47His Mutation in ADH2 Gene and chronic hepatitis B.Results1.There was no significant difference between chronic hepatitis B group and control group in terms of sex,age and smoking factors.But there was significant difference between two groups in terms of alcohol drinking and family history of chronic hepatitis B.2.The difference of the frequencies for ADH2 genotypes between chronic hepatitis B group(GG,GA,AA were 13.1%,48.4%,38.5%,respectively) and the control group(GG,GA,AA were 17.2%,42.6%,50.2%,respectively) was significant (P=0.014);The frequency of G allele in hepatitis B group(37.3%) was significant higher than that in the control group(28.5%)(P=0.005). 3.Compared with the carriers of homozygotes of the AA allele as the reference, the crude ORs with 95%CIs in the parentheses for the chronic hepatitis B were that 1.48(1.01-2.17)for the heterozygous carriers,and 2.38(1.24-4.59)for the carriers of homozygotes of the GG allele,respectively.The multivariate adjusted ORs were 1.46(0.97-2.19),and 2.51(1.25-5.02)for the heterozygous carriers,and for the carriers of homozygotes of the GG allele,respectively.4.There was interaction between Arg47His mutation in ADH2 Gene and alcohol drinking on the chronic hepatitis B.Based on the ORs,the measures of interaction as departure from additivity were as follows:the synergy index(S)was 1.90,the relative excess risk due to interaction(RERI)was 1.62,and the attributable proportion due to interaction(AP)was 36.64%.After the adjustment for the potential confounders,S was 2.08,RERI was 2.27,and AP was 42.22%.5.Using the case-only study,the multinomial logistic regression analysis indicated that there was also interaction as departure from multiplicative between Arg47His mutation in ADH2 Gene and hepatitis B virus reproduction on the chronic hepatitis B.The multivariate adjusted ORs were 1.10(95%CI:0.51-2.38)for the heterozygous carriers and 3.51(95%CI:0.93-13.32)for the carriers of homozygotes of the GG allele,respectively.Conclusions1.There is no significant association between age,sex,smoking and chronic hepatitis B.However,alcohol drinking and family history of hepatitis B were significant associated with chronic hepatitis B.2.Arg47His mutation in ADH2 Gene might serve as one of major risk factors to chronic hepatitis B in the Han nationality of China3.There was interaction as departure from additivity between Arg47His mutation in ADH2 Gene and alcohol drinking on the chronic hepatitis B.4.There was also interaction as departure from multiplicative between Arg47His mutation in ADH2 Gene and hepatitis B virus reproduction on the chronic hepatitis B.