| Objectives:Alcohol dependence syndrome(ADS),commonly known as alcohol dependence and alcohol addiction,refers to the special psychological state caused by repeated heavy drinking,which is manifested in the craving for alcohol and the compulsive experience of frequent drinking,which is the mental and physical dependence on alcohol caused by drinking.Alcohol dependence is a kind of chronic encephalopathy,a kind of mental disease and a major public health problem.The etiology and pathogenesis of alcohol dependence are still unclear,but the consensus is that multiple etiologies(biological,psychological,social environment,etc.)work together.Among them,the formation of alcohol dependence is most influenced by genetic factors,and more than half of drinking risk degree is determined by genetic factors.Therefore,it is of great significance to study the susceptibility genes of alcohol dependence for the prevention and treatment of alcohol dependence.The study found that the serotonin receptor gene polymorphism was associated with the risk of alcohol dependence syndrome.But the results are controversial among ethnic groups.At present,the conclusions of relevant studies on the Han population in Yunnan are inconsistent.Therefore,17 polymorphic loci of HTR1B,HTR2A,HTR3A,HTR3B and HTR7 genes were selected as research objects in this paper to explore the correlation between single nucleotide polymorphisms(SNP)of 5-HTR gene and alcohol dependence syndrome,and to look for the genetic risk loci of alcohol dependence in the Han population in Yunnan province,China.Methods:This study based on the Diagnostic and statistical manual of Mental disease 5 edition(Diagnostic&Statistic Manuel of getting Disorders V,DSM-V)Diagnostic criteria from Yunnan province alcohol and drug dependence treatment of hospital of Mental illness of hospitalized patients with alcohol dependence in selecting 100 cases as group,at the same time choose 60 cases with the matching set of healthy people as control group.The samples of case group and control group were all Han males from Yunnan province.5ml venous blood before elbow was extracted from each sample.Genomic DNA extraction kit was used to extract DNA.General fluorescence probe technology was used to detect the SNP typing of 5 genes and 17 SNP sites in the above 160 samples.SPSS 24.0,SHEsis and other software were used to analyze the results.Results:1.Hardy-Weinberg equilibrium test resultsIn the alcohol dependence group and healthy control group,there were 17 SNP loci of 5 genes(rsl 1568817,rsl30058,rs6296,rs2000292,rs6311,rs6313,rs4941570,rs1176713,rs10160548,rs33940208,rs1062613,rs3782025,rs2276305,rs11716403,rs11596518,rs7904560)genotype frequency distribution was consistent with the Hardy-Weinberg equilibrium(p>0.05).2.Results of unit point analysisIn the Han population in Yunnan province,except that rsl 1568817 in HTR1B gene and rs1062613 in HTR3A gene are correlated with alcohol dependence syndrome,the other SNP sites are not related to alcohol dependence syndrome.The allele frequency distribution difference of HTR1B gene rs11568817 between the two groups was statistically significant,and the allele frequency distribution of rs11568817 G in the case group was significantly higher than that in the control group(p=0.038,OR=2.174,95%CI:1.030～4.589).The genotype frequency distribution difference of HTR3A gene rsl062613 between the two groups was statistically significant,and the genotype frequency distribution of rsl062613 CT in the case group was significantly higher than that in the control group(p=0.037,OR=2.193,95%CI:1.048-4.366).In the recessive model of HTR1B gene rsl 1568817,the distribution of GT+GG genotype frequency in the case group was significantly higher than that in the control group(p=0.008,OR=2.824,95%CI:1.281-6.224).In the HTR3A gene rsl062613 dominant model,the CC genotype frequency of the control group was significantly higher than that of the case group(p=0.044,OR=0.432,95%CI:0.188～0.991).3.Linkage imbalance analysis resultsAnalysis of SHEsis software showed that there was a linkage imbalance between SNP sites of the above five genes.HTRIB gene rs6296 and rs11568817,rs2000292 and rsl 1568817,rsl30058 and rs6296,rsl30058 and rs2000292 were strongly linked to each other(D ’>0.8).rs130058 and rs11568817 are completely interlocked(D ’=1).HTR2A gene rs4941570 was strongly linked with rs6311,rs6313 each other(D ’>0.8).rs6313 and rs6311 are completely interlocked(D ’=1).HTR3A and HTR3B genes rsl 176713 and rsl062613,rsl0160548 and rsl062613,rs3782025 and rs1176744,rs2276305 and rsl 176744 were strongly linked to each other(D’>0.8).rsl 176713 and rsl0160548,rs3782025 and rs2276305 are completely interlocked(D ’=1).HTR7 genes rs7916403,rsll596518 and rs7904560 were completely linked(D ’=1).4.Haplotype analysis resultsHaplotypes of 16 SNP sites in HTR1B,HTR2A,HTR3A,HTR3Band HTR7 genes were analyzed,and the frequency of 19 haplotypes in the alcohol-dependent group or the healthy control group was greater than 0.03.Haplotype analysis showed that there was no significant difference in the haplotype distribution of 16 SNP sites of 5 genes between the alcohol dependent group and the normal control group(p>0.05).Conclusions:1.Among the Han population in Yunnan province,except that rsl 1568817 in HTRIB gene and rs1062613 in HTR3A gene are correlated with alcohol dependence syndrome,the other SNP sites are unrelated to alcohol dependence syndrome.Allele G of HTRIB gene rs11568817 may be a risk factor for alcohol dependence in Yunnan Han male population,and GT+GG genotype may increase the risk of alcohol dependence in rs11568817 stealth model.The HTR3A gene rsl062613 CT genotype may increase the risk of alcohol dependence,while the CC genotype may reduce the risk of alcohol dependence in the rs1062613 dominant model.2.There was linkage imbalance between SNP sites in HTR1B,HTRZA,,HTR3B and HTR7.There were linkage disequilibrium at rs1062613,rsl0160548 and rs1176713 in HTR3A.3.Haplotype analysis results showed that there was no significant difference in the haplotype distribution of 16 SNP sites of 5 genes between the alcohol dependent group and the normal control group(p>0.05). |
PDF Full Text Request