The Relationship Between Anhedonia And Polymorphism Of DRD3,TREK1 Gene In Depressive Patients

Objective : To explore the relationship between anhedonia and polymorphism of DRD3,TREK1 gene and analysis the possible genetic mechanism of anhedonia in depressive patients.Methods :All the 212 participants were evaluated by HAMD-24 and the Snaith-Hamilton Pleasure Scale(SHAPS).Participants meeting the below criteria were recruited into casegroup: the score of the HAMD-24 was higher than 21 and the score of the SHAPS was more than 3,the rest 102 mentally healthy volunteers,whose HAMD-24 and SHAPS scores were less than 8 and 3 respectively,were recruited as the control group.All of the subjects were Chinese north Han population and DNA was extracted from the blood samples of subjects.SNP(rs6280)in gene DRD3 and SNPs(rs12136349,rs2841608,rs2841616,rs10494996)in gene TREK1 were selected to be genotyped by sequencing techniques and the study of correlation between was performed with further analysis by SPSS 22.0software: the frequencies of different genotypes and alleles of SNPs were analyzed by chi-square;specifically,in the case group,the degree of anhedonia was evaluated by SHAPS,and then the differences of SHAPS scores were analyzed by one-way ANOVA;moreover,the distribution of different genotypes and alleles in discrepant degrees of anhedonia were analyzed by chi-square.In addition,the correlation between anhedonia and depression was analyzed by bivariate correlation analysis.P<0.05 was regarded as a criteria value for statistical significance.Results:1.The frequencies of the 5 SNPs were not deviated from the Hardy-weinberg equilibrium in all subjects(P>0.05),illustrating randomness of the collection and good representation of the samples.2.According to the bivariate analysis(r=0.090,P=0.352),the scores of SHAPS and HAMD showed no correlation.However,the multiple linear regression analysis revealed that the score of SHAPS was significantly associated with the retardation factor of HAMD3.There was no significant difference in the distribution of genotypes for4 loci of TREK1 gene and rs6280 of DRD3 gene between case group and control group.4.Within the 4 SNPs in TREK1 gene,only the frequency of allele A in rs12136349 in case group was significantly higher than that in control group(P=0.033).In addition,there was no significant difference between the two groups on rs6280 in gene DRD3.5.The significant difference in the degree of anhedonia was found between AG and GG genotype in rs12136349 of gene TREK1 within case group(P=0.028).As for rs2841616,the differences among different genotypes were significant(P=0.027)and the post-hoc test revealed that the degree of anhedonia of patients with GG genotype was significantly different from whose with AA and AG genotype(P=0.018 and P=0.012respectively).However,there were no differences among different genotypes of rs2841608 in TREK1 gene and rs6280 in DRD3 gene.6.After comparing the distribution of different genotypes between the high-degree anhedonia group and the low-degree group,the distribution with different genotypes was statistically significant on the loci of rs2841606(P=0.005)and rs2841616 in gene TREK1(P=0.001).Between these two groups,there was no statistical significance on the other two locus rs12136349 and rs10494996 in gene TREK1,as well as rs6280 in DRD3 gene.7.Comparison of the frequencies of different alleles between the different degree anhedonia groups showed that the distributions of alleles on the loci of rs2841606 and rs2841616 in gene TREK1 were statistically significant(P=0.010 and P=0.001 respectively).However,no significant difference between the two groups existed on the other two locus rs12136349 and rs10494996 in gene TREK1 and rs6280 of DRD3 gene.8.No statistical differences were found between male and female in the degree of anhedonia,the distribution of different genotypes and alleles of the five loci in TREK1 and DRD3 gene.8.No statistical differences were found between male and female in the degree of anhedonia,the distribution of different genotypes and alleles the of four loci in TREK1 gene and locus of rs6280 in DRD3 gene.Conclusion:1.The different alleles distribution of rs12136349 and rs2841616 in gene TREK1 may account for the genetic pathogenesis of depression.2.The severity of anhedonia was not associated with the degree of depression,thus it was hypothesized that anhedonia could be an independent symptom of depression.3.A allele of rs12136349 in TREK1 was associated with the occurrence of depression.And the correlation was not found between rs2841608,rs2841616 and rs10494996 SNPs and depressive disorder in TREK1 gene of Chinese north Han population,neither rs6280 in DRD3 gene.