Association Between 8 Susceptibility Genes Of Schizophrenia And The Risk Of Schizophrenia And The Efficacy Of Clozapine:Meta-analysis

Schizophrenia is one of the most serious mental diseases found in humans.Previous studies indicated that the single nucleotide polymorphism(SNP)in the gene DRD2,DRD3,DRD4,5-HT2A,COMT,MTHFR,ErbB4,NRGl was associated with schizophrenia.However,in the present study,some results were conflicting between the association SNP in the gene DRD2,DRD3,DRD4,5-HT2A,COMT,MTHFR,ErbB4,NRG1 and the risk of schizophrenia in Asian,Caucasian and other populations.Electronic search of some databases identified 17 case-control studies with available genotype frequencies of rs 1799732 of DRD2 for the meta-analysis,involving a total of 2871 cases and 4574 controls.A pooled odds ratio(OR)with 95%confidence interval(CI)was used to assess the association.The current meta-analysis showed an association between rs 1799732 and schizophrenia in Asian populations(P = 0.001,OR = 0.713,95%CI:0.580-0.878;P= 0.068 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.This meta-analysis included 4 case-control studies with available genotype frequencies of rs 1800955 of DRD4,involving a total of 876 cases and 924 controls.The current meta-analysis showed an association between rs 1800955 and schizophrenia in Asian populations(P = 0.004,OR = 1.217,95%CI:1.065-1.390;P= 0.786 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.23 case-control studies with available genotype frequencies of rs6313 of 5-HT2A were included in this meta-analysis,involving a total of 3707 cases and 3912 controls.The current meta-analysis showed an association between rs6313 and schizophrenia in Caucasian populations(P = 0.008,OR = 0.751,95%Cl:0.609-0.926;P= 0.318 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.Electronic search of some databases identified 6 case-control studies with available genotype frequencies of rs6267 of COMT for the meta-analysis,involving a total of 3096 cases and 3120 controls.The current meta-analysis showed an association between rs6313 and schizophrenia in Asian populations(P = 0.040,OR = 1.146,95%Cl:1.007-1.306;P=0.185 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.This meta-analysis included 7 case-control studies with available genotype frequencies of rs737865 of COMT,involving a total of 5459 cases and 3449 controls.The current meta-analysis showed an association between rs737865 and schizophrenia in other populations(P = 0.001,OR =0.820,95%Cl:0.733-0.918;P= 0.695 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.16 case-control studies with available genotype frequencies of rs1801131 of MTHFR were included in this meta-analysis,involving a total of 3777 cases and 5090 controls.The current meta-analysis showed an association between rs 1801131 and schizophrenia in Asian populations(P = 0.001,OR = 1.245,95%Cl:1.807-1.425;P=0.336 for heterogeneity)and Caucasian populations(P = 0.012,OR = 1.212,95%CI 1.042-1.408;P= 0.004 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.43 case-control studies with available genotype frequencies of rs1801133 of MTHFR were included in this meta-analysis,involving a total of 13848 cases and 18731 controls.The current meta-analysis showed an association between rs 1801131 and schizophrenia in Asian populations(P = 0.002,OR = 1.121,95%CI:1.043-1.206;P<0.001 for heterogeneity)and Caucasian populations(P = 0.014,OR = 1.124,95%CI:1.025-1.234;P= 0.008 for heterogeneity)and other populations(P = 0.000,OR = 2.140,95%CI:1.416-3.234;P= 0.504 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.Thus,the difference association in three populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates t.To validate the association between SNP of susceptibility genes and schizophrenia,further studies with larger participant populations worldwide are needed.This meta-analysis will investigate the association between rs6280 of DRD3 and rs6313 of 5-HT2A gene polymorphisms and the response of chlorpromazine treatment in schizophrenia.10 case-control studies with available genotype frequencies of rs6313 were included in this meta-analysis,involving a total of 687 responses and 551 non-responses.The current meta-analysis showed an association between rs6313 and the response of chlorpromazine treatment in schizophrenia with Asian populations(P = 0.009,OR = 1.377,95%CI:1.084-1.750;P= 0.784 for heterogeneity)and Caucasian populations(P = 0.018,OR=0.756,95%CI:0.599-0.952;P= 0.475 for heterogeneity).The Egger's test(P>0.05)and the Begg's test(P>0.05)are both suggestive of the lack of publication bias for the included studies.The rs6313 of 5-T2A gene may have important influence on clinical response of chlorpromazine treatment on schizophrenias.