| Objective:Alcohol dependence syndrome is a complex disorder which is influenced by physiological, psychological, environmental factors, individual inheritance and so on. Study indicates that hereditary factor plays a dominating role in the process of alcohol dependence pathogenesis which is one of the processes of polygenes heredity. In the study, we discuss the hereditary features of COMT (catechol-O-methyltransferse) gene in both alcoholic dependent group and healthy control group by detecting its exon, intron and another 2 candidate genes in 3',5'noncoding regions. We hope to reveal the genetic relevance between alcohol dependence syndrome and the four candidate genes in order to find out the etiopathogenesis of alcohol dependence syndrome and, so to provide scientific evidence to enhance genetic diagnosis and clinical therapy accordingly.Methods:According to the《Diagnostic and Statistic Manuel of Mental DisordersⅣ》(DSM-Ⅳ) diagnostic criteria, we select 107 alcoholic dependent patients of Mental Health Center of Yunnan Province and 214 normal persons as control group in the period during 2006-2009.200ul venous blood samples from each person of the alcoholic dependent group and healthy control group were obtained, DNA was extracted by phenol-chloroform method and polymorphism of the 4 candidate genes was assessed by detecting genotypes and allele frequencies by polymerase chain reaction and restriction fragment length technique (PCR-RFLP) in both groups. All data were analyzed by statistical software:SPSS 11.5, Arlequin, HWSIM and SHEsis.Results:There are two alleles(G,A) at gene locus rs2075507 and three genotypes (G/G,G/A,A/A) of COMT gene. Genotype G/G is found in 7 cases among alcoholic dependent group, which take up 6.5%. There are 46 cases with genotype G/A. 43%. A/A genotype is found in 54 patients that account for 50.5%. The frequency of allele G is 28.0% and the frequency of allele A is 72.0%. By the contrast, genotype G/G is found in 21 cases (9.8%), genotype G/A is found in 84 cases (39.3%), genotype A/A is found in 109 cases (50.9%) in control group. The frequency of G allele is 29.4%, the frequency of A allele is 70.6%.We discover two alleles(T,C) at gene locus rs73786 of COMT gene and three genotypes (T/T,T/C,C/C). In patients with alcoholic dependent syndrome, genotype T/T are found in 45 cases(42.1%), genotype T/C are found in 58 cases(54.2%), genotype C/C are found in 4 cases(3.7%), The frequency of T allele is 69.2% and the frequency of C allele is 30.8%. In healthy control group, genotype T/T are found in 120 cases(56.1%), genotype T/C are found in 73 cases(34.1%), genotype C/C are found in 21 cases(9.8%). The frequency of T allele is 73.1% and the frequency of C allele is 26.9%. There are two alleles(G,A) at gene locus rs4680 and three genotypes (G/G,G/A,A/A) of COMT gene. In patients with alcohol dependence syndrome, genotype G/G is found in 61 cases (57.0%), genotype G/A is found in 40 cases (37.4%), genotype A/A is found in 6 cases (5.6%). The frequency of G allele is 75.7%, the frequency of A allele is 24.3%. In control group, genotype G/G is found in 106 cases (49.5%), genotype G/A is found in 96 cases (44.9%), genotype A/A is found in 12 cases (5.6%). The frequency of G allele is 72% and the frequency of A allele is 28%. There are two alleles(G,A) at gene locus rs 16559 and three genotypes (G/G,G/A,A/A) of COMT gene. In patients with alcohol dependence syndrome, genotype G/G is found in 23 cases (21.5%), genotype G/A is found in 52 cases(48.6%), genotype A/A is found in 32 cases(29.9%). The frequency of G allele is 45.8% and the frequency of A allele is 54.2%.Compared with control group, genotype G/G is found in 34 cases(15.9%), genotype G/A is found in 112 cases(52.3%), genotype A/A is found in 68 cases(31.8%). The frequency of G allele is 42.1% and the frequency of allele A is 57.9%.The genotype frequencies of COMT gene at gene locus rs737865 differed significantly between alcoholic dependent group and control group(P＜0.05).The frequency of C/C genotype in control group is higher than alcoholic dependent group. Frequencies of rest genotypes and alleles in both alcoholic dependent group and control group have no statistical significant differences (P＞0.05). Logistic regression analysis indicates that C/C genotype was associated positively with alcoholic dependence syndrome(OR:0.822). but it has no statistical meaning (P＞0.05).The results of haplotype analysis for gene loci rs2075507, rs737865, rs4680, rs165599 reveal that there are 12 kinds of major haplotypes in Han majority of Yunnan province (frequency of each haplotype is greater than 1% at least in one group), A-C-A-A haplotype might be a factor leading to alcoholic dependence syndrome(P=0.003347,OR=2.865). Lingkage disequilibrium analysis shows that there is a strong linkage between rs2075507 and rs737865 in Han majority of Yunnan province (D＞0.8).Conclusion:There is no significant association of gene loci rs2075507, rs4680 and rs165599 between alcoholic dependent group and control group in Han majority of Yunnan province. However, rs737865 gene polymorphism is related to alcoholic dependence. The frequency of three genotypes at this gene locus has statistical significant difference (P＜0.05) in both alcoholic dependent group and control group. The frequency of genotype C/C in control group is higher than alcoholic dependent group, C/C genotype is associated positively with alcohol dependence. A-C-A-A haplotype might be a dangerous factor leading to alcohol dependence syndrome(P=0.003347,OR=2.865).There are strong linkage between rs2075507 and rs737865 in Han majority of Yunnan province (D＞0.8). |
PDF Full Text Request