A Study On Abnormally Expressed MiRNA Screening In Schizophrenia And The Association Analysis Of RABEP1 Polymorphisms And Weight Change

Objective: To verify miRNAs which were abnormally expressed in schizophrenia(SZ)and to further explore the role of miRNAs in the molecular pathogenesis of SZ.To explore the association between RABEP1 gene polymorphism and body weight changes induced by antipsychotic treatment.Methods: Real-time Quantitative polymerase chain reaction(RT-PCR)was used to validate differential expression of miRNAs in 78 patients with first-episode SZ and 75 healthy controls.The RABEP1 gene polymorphism was detected by TaqMan genotyping technology in 1701 first-episode schizophrenic patients.Patients were followed up for 2 weeks and the association between weight changes and RABEP1 gene polymorphism were analysised.ROC curve were used to assess the diagnostic value of SZ with plasma miRNA.Logistic regression was used to analyze the association between RABEP1 gene and weight change induced by antipsychotic drugs.Results: 17 differentially expressed miRNAs were screened out,and 16 differentially expressed miRNAs were further verified(miR-24,miR-146 a,miR-150,miR-197,miR-328,miR-146 b,miR-520a-3p,miR-886-5p,miR-320,miR-574-3p,miR-628-3p,miR-1243,mi R-663 b,miR-1274 a,miR-1274 b,miR-664).ROC curve analysis showed that 5 miRNAs had a high diagnostic value for SZ(AUC> 0.70 for all).Association analysis showed that there was no significant association between rs1058398 and rs1065482 of RABEP1 and weight changes in all patients.Stratification analysis indicated that in the patients treated with aripiprazole,the additive and dominant models of rs1058398 and rs1065482 were significantly associated with weight gain,OR(95%CIs)were 1.777(1.077-2.934)and 2.424(1.236-4.753),P values were 0.025 and 0.010 respectively.The OR(95%CIs)of dominant models were 2.182(1.123-4.242)and 2.393(1.161-4.929)and P values were 0.021 and 0.018 respectively.In the single drug group,the dominant model of rs1058398 was significantly associated with a weight decrease,OR(95%CIs)was 0.605(0.381-0.961)and P value was 0.033.In the combination therapy group,the rs1058398 dominant model was statistically correlated with the increase of body weight,OR(95%CIs)was 1.573(1.106-2.237),P value was 0.012.rs1058398 dominant model was significantly associated with weight gain,and OR(95%CI)was 1.372(1.002-1.880)and P value was 0.049 in the female population.rs1065482 addition model was significantly associated with weight gain,and OR(95% CI)was 1.408(1.033-1.918)and P value was 0.030 in the male population.The rs1065482 additional model was significantly associated with weight gain at age <35 years and OR(95% CI)was 1.356(1.017-1.809).Conclusions: miR-24,miR146 a,miR-150,miR197,miR-328,miR-146 b,miR-520a-3p,miR-886-5p,miR-320,miR-574-3p,miR628-3p,miR1243,miR-663 b,miR-1274 a,miR-1274 b,miR-664 are involved in the pathogenesis of SZ.rs1058398 and rs1065482 of RABEP1 are associated with weight gain due to antipsychotic treatment.The antipsychotic drugs,age and gender might modulate the genetic effect.Significant association of RABEP1 polymorphisms with weight gain was observed in SZ patients with aripiprazole treatment.