Prediction And Validation Of CRP Gene Polymorphisms In SSRIs Antidepressants Efficacy

Objective: Depression is extremely harmful.The current clinical treatment of depression mainly depends on the assessment of symptomatology,and trial-and-error treatment exists.Identification of highly sensitive and specific biomarkers for predicting efficacy can reduce disease delay and adverse reactions.Although accumulating evidence has demonstrated that antidepressants efficacy are positively associated with circulating C-reactive protein(CRP)levels,there are few studies on CRP gene polymorphisms and antidepressants efficacy.In this study,CRP single-nucleotide polymorphisms(SNPs)that influence CRP levels,are selected to predict and verify the antidepressants efficacy of selective serotonin reuptake inhibitors(SSRIs).We explored whether CRP SNPs are related to SSRIs antidepressants efficacy in Han Chinese patients.Methods: The study was divided into two parts,the first part recruited 113 patients with first-episode depression to explore CRP gene and antidepressants efficacy,the second part recruited 108 patients with first-episode depression to carry out the verification of previous studies.General demographic information and peripheral blood samples were collected,SSRIs drugs were selected for antidepressants treatment.Haploview software was used to screen genetic loci associated with CRP levels.DNA was extracted from whole-blood samples obtained from the cubital vein under fasting state.Following up for 6 weeks,clinical symptoms were evaluated by Hamilton rating scale for depression(HAMD17)at 0,2,4 and 6 weeks.The main efficacy indicators were HAMD17 scores at baseline and after 6 weeks.The correlation between CRP SNPs and antidepressants efficacy was performed using binary logistic regression analysis.The association of CRP SNPs and HAMD17 scores during follow-up was analysed using One-Way Repeated Measures ANOVA.SPSS24.0 software was used for statistical analysis.Genotype frequencies <0.01 were excluded.The level of statistical significance was set at p<0.05(two-tailed).Results: The first part 1.1 CRP SNPs general demographic information analysis CRP SNPs were compared by gender,age,education level,marital status and baseline HAMD17 total scores.There was significant difference in age for CRP rs1800947.There were not significant differences in general demographic data for CRP rs1130864,rs1205,rs2794521.1.2 CRP SNPs efficacy Analysis 1.2.1 One-site efficacy analysis Logistic regression analysis was conducted between CRP SNPs and SSRIs antidepressants efficacy.CRP SNPs were related to antidepressants efficacy.CRP rs1205 CC exhibited higher effective rate and remission rate.Similarly,CRP rs2794521 TT had lower effective rate and remission rate.1.2.2 Multi-site efficacy analysis CRP rs1130864-rs1205-rs1800947-rs2794521 was not correlated with antidepressants efficacy.1.3 CRP SNPs and HAMD17 scores during follow-up analysis A rs1205 genotype-time interaction was found in HAMD17 scores analysis.The second part 2.1 CRP rs1205?rs2794521 general demographic information analysis CRP rs1205 and rs2794521 in gender,age,education level,marital status and baseline HAMD17 total scores were not statistically significant.2.2 CRP rs1205?rs2794521 efficacy Analysis CRP rs1205 was not related to antidepressants efficacy in the effective,ineffective and remission,non-remission models.CRP rs2794521 was not related to antidepressants efficacy in the remission and non-remission model,but rs2794521 TT had lower effective rate in the effective and ineffective model.2.3 HAMD17 scores before and after treatment in CRP effective genotype Analysis: After antidepressants treatment,the scores of slow symptoms were not significant improvement and the remaining HAMD17 scores decreased significantly in depressed patients with CRP rs2794521 recessive allele.2.4 CRP rs1205 and HAMD17 scores during follow-up analysis A rs1205 genotype-time interaction was not found in HAMD17 scores analysisConclusion: 1 CRP rs2794521 may be a candidate inflammatory gene locus for predicting SSRIs antidepressants efficacy in Han depressed patients.2 Depressed patients with CRP rs2794521 recessive allele improved the depressive symptoms except slow symptoms after SSRIs antidepressants treatment.