| Part I Association Study of 5-HTR2A(-1438A/G) Promoter Region gene polymorphisms and Affective DisorderObject To explore the association between the 5-HTR2A (-1438A/G)promoter region gene polymorphisms and episode, gender, suicidality and subtypes of affective disorder in Chinese Han people.Methods Polymerase chain reaction (PCR) was used to detect the distributive frequency of serotonin 2A receptor promoter region polymorphisms of 160 affective disorder patients(patient group) and 160 normal people (control group) as well as PCR and sequencing skills were applied to detect the association between serotonin 2A receptor gene polymorphisms with episode. gender, suicidality and subtypes of affective disorder of 160 affective disorder patients and 160 normal people.Results 5-HTR2A(-1438A/G):①There were AA. AG, GG genotypes according to the two alleles of 513bp.331bp和182bp.②There were significant differences of the 5-HTR2A genotypes(χ2=6.503, P=0.039) and the alleles (χ2=4.025, P=0.045) between the patient group and the control group. The frequency of GG (38.7% vs. 34.4%),AG(47.5% vs. 40.6%) genotypes;and G allele (62.5% vs. 54.7%) in patients was higher than that in control group. Significant difference of allele frequency could be found (χ2=8.649, P=0.003) between women patients group and the control group.GG genotypes (40.9% vs. 21.9%) and G allele (63.3% vs. 47.3%) in women patients was higher than those in control group.But there was no significant difference between man patients and control group (p>0.05). There was no significant difference between Bipolar disorder(depressive phase)(χ2=0.012,p=0.994;χ2=0.005,p=0.946)with control group. Significant differences of genotypes(χ2=8.412,p=0.015) and allele(χ2=5.236.p=0.022) frequency could be found between the Unipolar depression patients and the control group. The insignificant differences could be found between the affective disorder patients with and without suicidality behavior either for the frequency of the genotypes(χ2=0.060,P=0.970) or that of the alleles(χ2=0.038,P=0.845). There was no significant difference about the distributive frequency of genotypes(χ2=1.384,P=0.501) and alleles(χ2=0.016.P=0.898) of 5-HTR2A between the different gender affective disorder patients with suicidality behavior.Conclusions 5-HTR2A(-1438A/G):5-HTR2A gene polymorphism related to the episode of affective disorder in northwest Chinese Han people,especially to the Unipolar depression. AG or GG or G may be the susceptibility genotypes or allele of the affective. There may be more women with G allele than men with it in patients with affective disorder.PartⅡAssociation Study of gene polymorphisms of 5-HTR2A (-1438A/G) and Paroxetine treatment response.Objective To explore whether the polymorphisms of 5-HTR2A(-1438A/G)was associated with the treatment response to Paroxetine.Methods All 136 Unipolar depression patients and 24 Bipolar disorder(depression phase) patients were treated with Paroxetine treatment for 4 weeks and evaluated with Hamilton Rating Scale of Depression (HAMD).Results The polymorphisms of 5-HTR2A(-1438A/G) were correlated with SSRls treatment response (F=6.317. P=0.013) There was significant difference of the effective power at the end of week 2(χ2=5.878, P=0.015). The effective power of AA,AG genotype was much higher than that of GG genotype(87.8%.57.6%,53.7%)and the effective power in the group with AA genotype was higher than that with AG genotype to the Unipolar depression patients.But the polymorphism of 5-HTR2A(-1438A/G) did not correlate with SSRIs treatment response (F=3.169,P=0.045) of Bipolar disorder(depression phase) patients.Conclusions Compared to others, the Unipolar depression patients with A allele of 5-HTR2A(-1438A/G) 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=5.878. P=0.015).To the contrary, the Bipolar disorder(depression phase) patients were not correlate with SSRIs treatment response.PartⅢAssociation Study of TPH(-703G/T) and TPH2(G1463A) gene polymorphisms and Affective DisorderObjective To explore the association between the TPH2(-703G/T)and TPH2(G1463A) gene polymorphisms and episode, gender, suicidality and subtypes of affective disorder in Chinese Han people.Methods Polymerase chain reaction (PCR) was used to detect the distributive frequency of TPH2 polymorphisms of 160 affective disorder patients(patient group) and 160 normal people (control group) as well as PCR and sequencing skills were applied to detect the association between TPH2 gene polymorphisms with episode, gender, suicidality and subtypes of affective disorder.Results 1.TPH2(-703G/T):①There were two alleles (G and T) and three genotypes (GG, GT,TT) and there fragmants (204bp,149bp,55bp) found.②There were no significant differences of the TPH2(-703G/T) genotypes (χ2=1.263,P=0.532) and the alleles (χ2=0.0;P=1.0) between the patient group and the control group. The insignificant difference of allele frequency could be found between not women patients but man patients with the control group (χ2=0.199,P=0.656;χ2=0.018,p=0.893). There was no significant difference between Bipolar disorder(depressive phase)(χ2=0.360,p=0.835)with cintrol group. Insignificant differences of genotypes(χ2=2.768,p=0.251) and allele(χ2=0.724.p=0.359) frequency could be found between the Unipolar depression patients and the control group. Insignificant differences of TPH2(-703G/T) genotypes(χ2=2.065,P=0.352)and the alleles(χ2=0.054.P=0.817) could be found in the Unipolar depression patients with and without anxiety. Meanwhile,there were no significant differences of TPH2(-703G/T) genotypes(χ2=0.432,P=0.860)and the alleles(χ2=0.110.P=0.740) between the affective disorder patients with and without suicidality behavior. There was no significant difference about the distributive frequency of genotypes(χ2=1.114,P=0.573) and alleles(χ2=0.048,P=0.827) of TPH2(-703G/T) between the different gender with suicidality behavior.2. TPH2(G1463A):No mutant A allele could be found in this study, we used the specific primers,but we only found GG genotype.Conclusions 1.Probability TPH2(-703G/T) gene polymorphism was no associated with affective diaorder.But it is not the final outcome.we can use another experimental methods .2.TPH2(A1463G):May be due to the different ethnic.after we expanded the samples size,howere,we did not find the mutant (1463A) allele in Chinese Han people. |
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