Study On The Relationship Between Alcohol Dependence Syndrome And Alcohol Metabolism-related Gene Polymorphisms

ObjectiveAlcohol dependence syndrome (ADS) commonly known as alcohol dependence, alcohol addiction, is a serious complex disease caused by alcohol abuse;Its occurrence, development and symptoms are subject to multiple factors such as heredity, psychology and environment.Family survey and twin studies indicated that genetic factors play an important role during the formation of the alcohol dependence. By studying for related gene polymorphisms, a lot of genes have been confirmed associatation with alcohol dependence, but there is still some controversial. In addition, results of studies also differences in different regions and ethnic groups.At present, the majority of domestic research only focused on Han nationality, minorities rarely. In this study,7polymorphic loci of alcohol metabolism-related gene were analyzed in the alcohol dependence group and the control group in miao and yi populations of yunnan, aiming to find the genetic relationship between the7polymorphic loci candidates and the alcohol Dependence Syndrome in the miao and yi populations of Yunnan and to provide a theoretical basis for the prevention, diagnosis and personalized treatment of alcohol dependence.MethodAccording to the diagnostic standards written in Diagnostic&Statistic Manuel of Mental Disorders IV, DSM-IV,30alcoholics of miao population and110alcoholics of yi population as samples for the alcohol dependence groups, correspondingly107healthy people of miao population and333healthy people of yi population were selected as samples for the control groups. Phlebotomize200μl blood from each sample and obtain DNA through saturated phenol-chloroform extraction. Use PCR-RFLP detect the genotype and allele frequencies of the7loci candidates for both alcohol dependence group and the control group. Perform statistical analyses using softwares like SPSS17.0, Haploview, HWSIM and SHEsis.Results1. The result of single locus analysisThree SNPs of the ADHIB rs2066702and rs75973598and the ALDH2rs671detected only one allele and one genotype in alcohol dependence group and the control group.There was no significant association of rs3813867、rs6413432and rs2070676of CYP2E1gene between alcohol dependent group and control group in miao Population of Yunnan. There also was no significant association of rs3813867、 rs6413432of CYP2E1gene and of rs698of ADH1C between alcohol dependent group and control group in yi Population of Yunnan. However, rs2070676might be associated with alcohol dependent patients in yi populatin. The A1A1、A1A2and A2A2genotype frequencies are1.8%、53.6%、44.6%in the alcohol dependence group and3.4%、31%、65.6%in the control group. Such genotype distributions are significantly different (X2=18.23, p<0.001) between the two groups. The A1and A2allele frequencies are28.6%,71.4%in the alcohol dependence group and18.9%,81.8%in the control group. Distributions of Al and A2alleles are significantly different (X2=9.288, p=0.002) between the two groups. People with A1A1and A1A2genotypes have a significantly higher relative risk of becoming alcohol dependent than those withA2A2genotype.2.The result of haplotype analysisWe construct8haplotypes through haplotype analysis of rs3813867, rs6413432, rs2070676of CYP2E1gene in the miao population of Yunnan, among which7haplotypes with frequencies over0.01in the alcohol dependence group or the control group.The total test showed there were no significant differences in the GABRA2gene polymorphisms between alcoholics and controls.we also construct8haplotypes through haplotype analysis of rs3813867, rs6413432, rs2070676of CYP2E1gene in the yi population of Yunnan, among which7haplotypes with frequencies over0.01in the alcohol dependence group or the control group.The total test showed there were significant differences in the CYP2E1gene polymorphisms between alcoholics and controls. People with H7(GTG) haplotype might have a higher risk of becoming alcohol dependent and people with H5(GAG)、H6(GTC) haplotypes have a lower risk of becoming alcohol dependent.3.The result of the allele and genotype distribution in the control group between Miao population and Yi populationThe allele and genotype frequencies of rs3813867in CYP2E1gene were significantly different between Miao population and Yi population, the c2allele frequency in Miao population was significantly higher than in Yi population; The allele and genotype frequencies of rs6413432in CYP2E1gene were significantly different between Miao population and Yi population, D allele frequency inYi population was significantly higher than miao population; The allele and genotype frequencies of rs2070676in CYP2E1gene is the similarity between between Miao population and Yi population.4.The result of linkage disequilibrium analysisIn miao population,there is strong linkage disequilibrium (D’>0.8) between rs6413432and rs2070676,but there is stronger linkage disequilibrium (D’=O.99>0.8)in alcohol dependence group; However,There is no strong linkage disequilibrium (D’<0.8) among rs3813867and rs6413432or2070676. In miao population,There is no strong linkage disequilibrium (D’<0.8) among3SNPs(3813867,rs6413432,rs2070676),But there is strong linkage disequilibrium (D’=0.99>0.8) between rsrs6413432andrs2070676in alcohol dependence group.ConclusionThere was no significant association of rs3813867、rs6413432and rs2070676of CYP2E1gene between alcohol dependent group and control group in miao Population of Yunnan. There also was no significant association of rs3813867^rs6413432of CYP2E1gene and of rs698of ADH1C between alcohol dependent group and control group in yi Population of Yunnan.The genotype A1A1or A1A2of rs2070676may be a genetic factor that responsible for increasing susceptibility of AD in yi population, A1allele may be a risk factor for alcohol dependence,and play a role in the occurrence of alcohol dependence.People with H7(GTG) haplotype might have a higher risk of becoming alcohol dependent and people with H5(GAG)、H6(GTC) haplotypes have a lower risk of becoming alcohol dependent.The c2allele frequency of rs3813867in Miao population was significantly higher than in Yi population;D allele frequency of rs3813867in Yi population was significantly higher than miao population; The allele and genotype frequencies of rs2070676in CYP2E1gene is the similarity between between Miao population and Yi population.There are strong linkage (D’-0.99>0.8) between rs6413432and rs2070676in alcohol dependence group of both miao and yi populatons.