Study On The Relationship Between Dopamine Gene Polymorphism And Alcohol Dependence Syndrome In Yunnan Yi Population

Objective:Alcohol Dependence (AD) is a complex disorder which is influenced by many factors.Its occurrence, development and symptoms are subject to multiple factors such as heredity, psychology and environment. Studies indicate that hereditary factor plays a dominating role in the process of AD pathogenesis.A series of studies on genes related to AD has shown that Dopamine gene polymorphism has something to do with the risk of becoming alcohol dependent. However, this result is still disputable among population of different races. In this study,5polymorphic loci of Dopamine gene were analyzed in the alcohol dependence group and the control group, aiming to find the genetic relationship between the5polymorphic loci candidates and the Alcohol Dependence Syndrome in Yunnan Yi Population, and to provide a theoretical basis for the exploration of AD pathology, gene diagnosis and treatment.Method:According to the diagnostic standards written in The International Statical Classification of diseases and Related Health Problems10th Revision,ICD-10,110alcohol dependence group from the Department of Alcohol and Drug Dependence in Yunnan Psychiatric Hospital clinicians screening by clinical phenotype and drinking history,and correspondingly330cases were selected gender ethnicity and ageas samples for the control group. Above samples by our group and the Department of Alcohol and Drug Dependence in Yunnan Psychiatric Hospital clinicians screening, between year2008and2011were selected as samples in Yunnan Shilin Yi Autonomous County area inhabited villages.Phlebotomize200μl blood from each sample and obtain DNA through saturated phenol-chloroform extraction. Use PCR-RFLP and PCR-VNTR techniques to detect the genotype and allele frequencies of the5loci candidates for both alcohol dependence group and the control group. Perform statistical analyses using softwares like SPSS17.0and SHEsis. Results:1.The result of Hardy-Weinberg equilibrium testThe observed frequences (TaqIA、TaqIB、-141CIns/Del) of DRD2and DRD4gene are associated with theoretical values between case and control groups, in line with the Hardy-weinberg balance rule.Addition to the observed frequences of DAT gene frequencies are associated with theoretical values in alcohol-dependent group deviation from Hardy-weinberg balance rule (P<0.05),the healthy control group genotype in line with the Hardy-weinberg balance rule.2. The result of single locus analysisThere was no significant association of TaqIB and-141CIns/Del of DRD2,DRD4and DAT gene between alcohol dependent group and control group in Yunnan Yi Population. However, TaqIA might be associated with alcohol dependent syndrome.The Al/Al, A1/A2and A2/A2genotype frequencies at TaqIA of DRD2gene are0.409、0.436、0.155in the alcohol dependence group and0.127、0.497、0.376in the control group. Such genotype distributions are significantly different (X2=46.365, p<0.001) between the two groups. The A1and A2allele frequencies at TaqIA of DRD2gene are0.627、0.376in the alcohol dependence group and0.373.0.624in the control group. Distributions of G and A alleles are significantly different (X2=42.390, P<0.001, OR:2.796) between the two groups. People with A1allele at TaqIA of DRD2gene have a significantly higher relative risk of becoming alcohol dependent than those with A2allele.3.The result of haplotype analysiswe construct8haplotypes through haplotype analysis of TaqIA、TaqIB、和-141CIns/Del of DRD2gene in the Yi nationality of Yunnan.The total test showed there were significant differences in the DRD2gene polymorphisms between alcoholics and controls. People with A1-B1-DEL、A1-B1-INS and A1-B2-INS haplotypes maybe higher risk factor alcohol dependent (p<0.05,0R>l)and people with A2-B1-DEL、A2-B1-INS and A2-B2-INS haplotypes maybe a protective factor to alcohol dependence syndrom in Yunnan Yi Population.(p<0.05,OR<1).4. The result of linkage disequilibrium analysis There is no strong linkage disequilibrium (D’<0.8) between TaqIA、TaqIB、-141CIns/Del、 DRD4and DAT in Yunnan Yi Population.Conclution:There was no significant association of TaqIB and-141CIns/Del of DRD2,DRD4and DAT gene between alcohol dependent group and control group in Yunnan Yi Population. However, TaqIA might be associated with alcohol dependent patients. There was significant association genotype and allele frequencies between alcohol dependent group and control group in Yunnan Yi Population. People with Al allele at TaqIA of DRD2gene have a significantly higher relative risk of becoming alcohol dependent than those with A2allele. People with A1-B1-DEL、A1-B1-INS and A1-B2-INS haplotypes maybe higher risk factor alcohol dependent (p<0.05,OR>1)and people with A2-B1-DEL、A2-B1-INS and A2-B2-INS haplotypes maybe a protective factor to alcohol dependence syndrom in Yunnan Yi Population.(p<0.05,OR<1).