| Objective:By applying Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF),5-HT3 Genes Polymorphisms were tested in alcohol dependence patients and general population, and compare the difference of genotype and allele. The general information questionnaire and some social psychological scales were also used to assess the personality character, social function, adaptive capacity and family condition etc。Try to find the high risk biological-genetic basis and psychosocial factors of the disease, so as to give some new ideas for alcohol addiction mechanism research and find new methods for its therapeutic interventions.Methods:21 loci of 5-HT3 were selected as study sites which were rs 1182457; rs11604247;rs1176713;rs10789980;rs10160548; rs897685; rs2276302;rs1062613; rs1176719;rs2795805;rs1672717;rs12421126; rs4938056; rs2276305;rs10789970; rs3758987; rs1176744; rs3782025; rs3831455; rs1176746; rs1176722. Byusing MALDI-TOF, amplified the area which located the two parts of known DNA sequences, and using restriction fragment length polymorphism (RLFP) to detect the genotypes and the frequency of the allele of 103 Chinese male alcohol dependence patients (study group).106 Chinese healthy males were selected as control group were detected the genes as well. The study group was selected from the inpatients in Shandong Mental Health Center from Mar.2013 to May 2014 whom were diagnosed as alcohol dependence according to ICD10 criteria and confirmed the diagnose by the consultant. The patients were stopped alcohol drinking for at least 2 weeks, and excluded the patients with severe physical and mental problems, who were all Chinese Han males, age from 18 to 60 years old. The control group was chose randomly, all were healthy Chinese Han male, no severe physical and mental problems. Compare the frequency distribution difference of 5-HTR3receptor genes of the two groups. And analyze every genotype and allele of the two groups, tried to find the sites which relevant to the disease. Inspected the linkage disequilibrium, and analyze the whole genetic relevance with the disease. The survey tools included general information questionnaire, EPQ, SSRS, FES-CV, which assess the psychosocial status. Two groups were instructed to do the papers by psychiatric staff, and signed the informed consents. The statistical methods include:genotype analysis, genotype and ALLelic frequency calculation which include three methods:a) single SNP relevant analysis, by using Pearson square test or Fisher to analyze the difference of every genotype and allele of the two groups, to find the relevant sites of the disease;b) Linkage disequilibrium (LD) analysis,:LD were measured by D’/r2; c) haplotype analysis: investigate the association of the overALL genetic haplotype with the disease through Pearson chi-square inspects, all statistical analysis of the general data and scales used were performed by using SPSS20.0 software. Chi square test, independent sample test, variance analysis, Logistic regression analysis were applied in this study. The difference was statisticALLy significant at P<0.05.Results:1. The frequency of distribution of 5-HT3 of the two groups are different by using Chi-square analysis:the rs3831455 which carried G allele, the rs11604247 which carried T allele and the genotypic frequency distribution are different (X2=4.082, p< 0.05 and X2=5.242, p< 0.05 respectively). The frequency of the rs3831455 which carried G ALLele and the rs11604247 which carried T allele are significant higher in patients group than control group (OR=1.586, L95=1.012, U95=2.488, p< 0.05 and OR=1.908, L95=1.09, U95=3.34, p< 0.05 respectively) The frequency of rs3831455 which carried G allele and rs11604247 which carried T allele is different in two groups by Logistic Regression analysis. (OR=1.591, L95=1.01, U95=2.506, STAT=2.004, p< 0.05 and OR= 1.829, L95=1.058, U95=3.162, STAT=2.161, p<0.05 respectively) LD and haplotype analysis:The frequency of TAG,TCTGTT and CTGAA of haplotype are significant different in two groups(x2=4.082, x2=6.504 and x2=5.916 respectively)2.The number of emotional instability and tend to be unstable in patients group is much more than control group(p< 0.05). The patients are more extravert type, and less middle type, and more typical psychoticism of P dimension. The result showed that the P and N personalities are more prevalent in alcohol dependence patients than healthy people. The difference is statisticALLy significant.(p< 0.05)3.The result of social support showed that:the score of social support is much lower in patients group which include the general, objective and perceived social support. The usage degree of the support is significant lower as well (P<0.05).4.The result of family environment showed that, the score of four factors which are emotional expression, intimacy, organization and achievement orientation, are much lower in patients group, and the score of contradiction and controlling are much higher in patients group.(p< 0.05)Conclusion:1.In patients group, the frequency of distribution of the rs3831455 which carried G allele and rs 11604247 which carried T allele in 5-HTR3 are higher and OR>1 by Chi-square analysis, this suggests that the rs3831455 which carried G allele and the rsl 1604247 which carried T allele are pathogenic factors of being alcohol dependence. In patients group, the frequency of the rs3831455 which carried G allele and rs11604247 which carried T allele in 5-HTR3A and 5-HTR3B are significant different by Logistic Regression analysis, STAT>0, this suggests that there are negative correlations between alcohol dependence and the rs3831455 which carried G allele and rs11604247 which carried T allele. In patients group, LD and haplotype analysis showed that the frequency of TAG,TCTGTT and CTGAA of haplotype are significant different in two groups. This suggests that TAG, TCTGTT and CTGAA of haplotype in 5-HTR3 are the susceptible factors of alcohol dependence.2.There are some relations between alcohol dependence and personality characters. Unhealthy personality characters may increase the risk of alcohol dependence;3.Poor social support is one of the risk factors of alcohol dependence. The score of social support is significant lower in patients group which include the general, objective, perceived social support and the usage degree of the support.4.Poor family environment may play an important role in forming alcohol dependence. the score of emotional expression, intimacy, organization and achievement orientation are much lower, and the score of contradiction and controlling are much higher in patients group. From the other side, this result also reflects that the families of the alcohol dependence patients are lack of flexibility, stiff, inattentive and contradictoriness. |
PDF Full Text Request