Association Study Of 5-HTT, 5-HTR1A And TPH₂ Gene Polymorphisms With Depression And Paroxetine Treatment Response In Chinese Han People

Partâ… Association Study of 5-HTT,5-HTRIA(C-1019G)and TPH₂(G1463A) Gene Polymorpbisms and DepressionObjective To explore the association between the 5-HTTLPR,5-HTR1A (C-1019G)and TPH₂(G1463A)gene polymorphisms and episode,gender,level or suicidal behavior of depression in Chinese Han people.Methods Polymerase chain reaction(PCR)was used to detect the distributive frequency of serotonin transport gene-linked promoter region polymorphisms of 150 depressive patients(patient group)and 150 normal people(control group)as well as PCR and sequencing skills were applied to detect those of serotonin 1A receptor and TPH2 gene polymorphisms of 150 depressive patients and 150 normal people.Results 1.5-HTTLPR:â‘ There were SS,LS,LL genotypes according to the two alleles of 375bp(S)and 419bp(L).â‘¡There were obvious differences of the 5-HTTLPR genotypes(χ²=6.199,P=0.045)and the alleles(χ²=5.238,P=0.022) between the patient group and the control group.The frequency of SS(26.0%; 20.0%),LS(52.7%;46.0%)genotypes;and S allele(52.3%;43.0%)in patients was higher than that in control group.Significant difference of allele frequency could be found(χ²=4.197,P=0.040)between women patient group and the control group.The frequency of S allele(55.3%;43.6%)in women patients was higher than that in control group.There was no significant difference between different leveled depression(χ²=3.420,P=0.181;χ²=3.226,P=0.072).The significant differences could be found between the depressive patients with and without suicidal behavior either for the frequency of the genotypes(χ²=6.056,P=0.048)or that of the alleles (χ²=5.511,P=0.019).The frequency of SS genotype(37.3%;20.2%)and S allele (61.8%;47.5%)in suicidal patients was higher than that in non-suicidal ones. There was no significant difference about the distributive frequency of genotypes (χ²=0.213;P=1.000)and alleles(χ²=0.087;P=0.768)of 5-HTTLPR between the different gender depressive patients with suicidal behavior.There was significant difference in frequency of genotypes and alleles(χ²=9.611,P=0.008;χ²=7.664, P=0.006)between different depressive levels with suicidal behavior.The frequency of SS genotype(42.5%;18.2%)and S allele(68.7%;36.4%)in major depressive patients with suicidal behavior was higer than that in moderate ones.2.5-HTRIA:â‘ It was found that there were two alleles(C and G)and three genotypes(CC,CG, GG).â‘¡There were significant differences of the 5-HTRIA(C-1019G)genotypes (χ²=6.990,P=0.030)and the alleles(χ²=7.112,P=0.008),between the patient group and the control group.The significant difference of allele frequency could be found between women patients and the corresponding control group(χ²=4.056,P=0.044). The frequency of G allele in major depression was higher than that in moderate (19.8%;15.3%).Significant differences of 5-HTR1A genotypes(χ²=7.305, P=0.019)and the alleles(χ²=6.835,P=0.009)could be found in the patients with and without suicidal behavior.To the patients with suicidal behavior,the significant differences of genotypes and alleles(Male:χ²=6.715,P=0.020;Female:χ²=4.449, P=0.035)were associated with gender.The women frequency with suicide of GG genotype(6.5%;5.0%)and G allele(33.9%;15.0%)was higher than that of men.3. TPH₂(G1463A):No mutant(1463A)allele could be found in this study so there was only GG genotype.Conclusions 1.5-HTTLPR:The frequency of SS genotype and S allele may be associated with episode and suicidal behavior of depression in Chinese Han people. There are more women with S allele in patients with depression.The patients with major depression,with SS genotype,would have more suicidal behaviors than those with other genotypes.2.5-HTR1A:The frequency of GG genotype may be associated with episode and suicidal behavior of depression in Chinese Han people. There may be more women with G allele than men with it in patients with depressive disorders and the women with GG genotype will have more suicidal behaviors.The association with disease's level and polymorphisms of serotonin 1A receptor should be studied further for it has not been discovered at present.3.There may not be the mutant(1463A)allele in Chinese Han people.It is not the final outcome and need to be testified in large samples.Partâ…¡Association Study of Gene Polymorphisms of 5-HTTLPR and 5-HTR1A (C-1019G)and Paroxetine Treatment Response.Objective To explore whether the polymorphisms of 5-HTTLPR and 5-HTR1A (C-1019G)were associated with the treatment response to Paroxetine.Methods All 150 depressive patients were treated with Paroxetine treatment for 8 weeks and evaluated with Hamilton Rating Scale of Depression(HAMD).Results 1.The polymorphisms of 5-HTTLPR were correlated with SSRIs treatment response(F=7.983,P=0.005).There was significant difference of the effective power at the end of week 2(χ²=13.662,P=0.001).The effective power of LL,LS genotype was much higher than that of SS genotype(68.8%,58.2%,28.8%) and the effective power in the group with LL genotype was higher than that with LS genotype.2.The polymorphism of 5-HTR1A(C-1019G)was correlated with SSRIs treatment response(F=3.169,P=0.045).2.There was significant difference of the frequency of the effective power at the end of week 2,week 4 and week 8(χ²=48.708, P=0.000;χ²=8.955,P=0.003;χ²=4.206,P=0.040).The outcome showed that the effective power with G allele at the end of week 4 was almost equal to that without G one at the end of week 2(69.4%:69.3%)and the effective power with G allele at the end of week 8 was lower than that without G one at the end of week 4(83.7%: 89.1%).Conclusions 1.Compared to others,the patients with L allele of 5-HTTLPR show a significant response to Paroxetine and there is significant difference of the frequency of the effective power at the end of week 2(χ² =13.662,P=0.001).2. The polymorphism of 5-HTR1A(C-1019G),G allele may be correlated with poor response and may result in late response to Paroxetine.