ABCB1Gene Polymorphisms Are Associated With The Severity Of Major Depressive Disorder And Its Response To Treatment

Objective:l.To probe the role in major depressive disorder genetic mechanism of the six SNPs (rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, rs2235015) of ABCB1gene by exploring the association between them and major depressive disorder.2. To prove the predictive biological items of personal treatment of major depressive disorder by investigating the association between the six SNPs(rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, rs2235015) of ABCB1gene and the therapeutic response.Methods:1.With the case-control design,292major depressive disorder patients who met DSM-IV criterion and208controls were matched in the ratio of age and gender. The relationship between the six SNPs and major depressive disorder were analyzed. The ligase detection reaction was used to detect the SNPs of rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, rs2235015.2.292major depressive disorder patients were given antidepressant drugs for six weeks (SSRIs: citalopram, parxetine, sertraline, SNRIs:venlafaxine, dutoxetine). They were elevated by Hamiltion Depression Scale (HAMD-17items). The patients were divided into two groups of the responder group and the non-responder group after six weeks, according to the decreasing rate of score of HAMD≥50%and<50%respectively. The differences of the six SNPs polymorphisms and the clinical factors between the responder group and the non-responder group were analyzed.3. All analyses were conducted with SPSS17.0for Windows.We used t-test, chi-square test, repeated measurement design chi-square analysis, logistic regression analysis, and odds ratio according to the type of the data. The haplotype model was constructed with SHEsis on-line.Results:1.rs2032582and rs1128503between patient group and control group, the differences in genotype distribution has no statistical significance (P>0.05), and there has a significant difference in the allele frequency distribution (P=0.03<0.05).2. Using haplotype analysis, rs1045642and rs2032582were in strong linkage disequilibrium (D’=0.8, r2=0.47). The proportion of individuals with the rs1045642-rs2032582haploid genotype was significantly different between case and control.3. rs2032583between responder group and Non-responder group, there has a significant difference in genotype or allele distribution (P<0.05).4. In the SSRIs therapy group, there has no significant difference in genotype or allele distribution between responder group and Non-responder group (P>0.05).5. In the SNRIs therapy group, rs2032583has a significant difference in genotype or allele distribution between responder group and Non-responder group (P<0.05).Conclusion:1.The rs2032582and rs1128503of ABCB1gene may be related with the major depressive disorder.2. The rs2032582-rs1045642of ABCB1gene polymorphisms may be related with the major depressive disorder.3. ABCB1gene polymorphisms may be no associated with the treatment response to SSRIs, but not SNRIs. TT genotype is likely to be a predictive factor of the better treatment response to SNRIs.13figures,49tables,35references...