Association Study Of Gene Polymorphisms In GABRA2 And OPRM1 With Alcohol Dependence In Shandong Province Han Men

Objective: Alcohol dependence(AD)is a common and complex mental disease in psychiatry.At present,the genetic polymorphism associated with alcohol dependence has been studied widely,but the relationship between AD and genetic polymorphisms has not been reached an agreement.In our study,the relationship between GABRA2 and OPRM1 gene polymorphisms and alcohol dependence is going to be further studied by a case-control in Shandong province Han men.This study is expected to give the pathogenesis,prevention,diagnosis and treatment timely of AD with genetics and scientific evidence.Methods: In the case-control study,200 Shandong province Han men diagnosted AUD by the Diagnostic and statistical Manual of Mental Disorders(DSM-5)came from the alcoholic abstinence Department of Daizhuang hospital in Shandong Province,and 200 DNA sample of healthy Han men in Shandong province obtained from the sample bank of Jining Medical College.DNA was extracted for PCR and Sanger gene sequencing.The relationship between the genotypes and alleles of SNPs(GABRA2 SNPs rs279858 and rs279844,OPRM1 SNPs rs1799971 and rs3778150)and alcohol dependence was analyzed after a series of experimental methods.The statistical analysis of sample was computed by the SPSS 22.0 software.T-test of independent sampler was used to analysis continuous quantitative datas which are considered to obey the normal distribution;The assessment of Hardy Weinberg equilibrium was performed by using the chi square test to compare the difference between the actual frequency and the theoretical frequency of the genotype;chi square test was used to determine differences in the frequency of genotype or allele between the alcohol dependent group and the healthy control group.Additive unconditional logistic regression was used for the association analysis of significant SNPs genotypes with alcohol dependence.The significant level ? is 0.05.Results:1.Basic information: In this study,we enrolled total 400 subjects,including 200 alcohol dependent patients and 200 control.The age in alcohol dependence group was(46.205±9.388)years,and the age in healthy control group was(44.465 ±8.789)years.T-test of independent sampler showed that no significant differences in age were observed in the two groups(t=-1.913,p =0.056).2.Hardy-Weinberg equilibrium expectation: The genotype frequencies of GABRA2 rs279858 did't deviate from HWE in control group,but deviated from HWE in alcohol dependent group(p =0.040).The genotype frequencies were consistent with HWE for other SNPs examined for both subject groups.3.Analysis of gene polymorphism difference between AD group and control group:The genotype frequencies distribution of GABRA2 SNPs rs279858 and rs279844 were significantly difference between AD group and control group(? 2 = 10.095,p = 0.006 and ? 2 = 11.208,p = 0.004,resp.).However,there were not significant difference in allele frequencies distribution of GABRA2 SNPs rs279858 and rs279844 between AD group and control group(p = 0.085,p = 0.056,resp.).It is suggested that the genotypes of GABRA2 SNPs rs279858 and rs279844 may be related to alcohol dependence.And the allele and genotype frequencies distribution of the OPRM1 SNPs rs1799971 and rs3778150 were not observed significant difference in AD group and control group(p >0.05).4.Logistic regression analysis: In the codominant genetic model,at rs279858,the risk of TC genotype carriers with AD was lower significantly than CC genotype carriers(p =0.002,OR=0.480).However,there was no significantly correlation between the risk of AD and TT genotype compared to CC genotype.At rs279844,the risk of AT genotype carriers with AD was lower significantly than TT genotype carriers with AD(p =0.001,OR=0.480).But there was no significantly association between the risk of alcohol dependence and AA genotype compared to TT genotype.Similarly,in the recessive genetic model,at rs279858,the risk of mutant genotype CC carriers with AD was 1.927 times as higher as T allele carriers(p = 0.002,OR = 1.927);At rs279844,the risk of mutant genotype TT carriers with AD was 1.988 times greater than A allele carriers(p = 0.001,OR = 1.988).The two genetic models suggested that CC genotype of rs279858 and TT genotype of rs279844 may be the susceptible factors of alcohol dependence.In addition,the interaction model of rs279858 and rs279844 showed that the risk of rs279858 genotype CC carriers with AD was 5.208 times higher than T allele carriers in the population with rs279844 A allele;the risk of rs279844 genotype TT carriers with AD was 3.422 times higher than A allele carriers in the population with rs279858 T allele.the risk of rs279858 mutant genotype CC carriers with AD was 0.580 times lower than T allele carriers in the population with rs279844 mutant genotype TT;And the risk of rs279844 mutant genotype TT carriers with AD was 0.381 times lower than A allele carriers in the population with rs279858 mutant genotypeCC.The risk of AD in the population with rs279858 genotype CC and rs279844 genotype TT simultaneously was 1.986 times higher than someone else.Conclusion :1.In Shandong province Han male population,the SNP loci rs279858 and rs279844 of GABRA2 may be related to alcohol dependence,and rs279858 genotype CC and rs279844 genotype TT may be the susceptible factor of alcohol dependence.In addition,the susceptibility of alcohol dependence may be influenced by the interaction of rs279858 and rs279844.2.In our study,no relationship was found between OPRM1 SNPS rs1799971 or rs3778150 and alcohol dependence in Shandong province Han men.