Associating Study Of COMT,5-HT2A,ApoE,CYP2D6 Gene Polymorphism And Refractory Schizophrenia

PartⅠ:Associating study of COMT gene polymorphism and refractory schizophreniaObjective:①To compare the genetic polymorphisms of catechol-O-methyltransferase(COMT)between refractory and nonrefractory schizophrenics in Han nationality.②To compare the genetic polymorphisms of COMT between positive family history schizophrenia and negative family history schizophrenia in Han nationality.③To compare the genetic polymorphisms of COMT between positive schizophrenia and negative schizophrenia in Han nationality.Method:105 non-refractory schizophrenia patients,121 refractory schizophrenia patients,63 positive family history schizophrenia,113 negative family history schizophrenia,115 positive schizophrenia,63 negative schizophrenia were recruited into the study.The gene polymorphism of COMT in all subjects was genotyped directly with polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP)technique,and to compare the differences of COMT polymorphism between refractory and non-refractory schizophrenia,positive family history schizophrenia and negative family history schizophrenia, positive schizophrenia and negative schizophrenia.Results:①The frequencies of COMT genotype G/G in non-refractory schizophrenia group(61.0%)were significantly more prevalent than that in refractory schizophrenia group(44.6%).②There were no significant differences between positive family history schizophrenia and negative family history schizophrenia in the frequencies of gene for COMT.③There were no significant differences between positive schizophrenia and negative schizophrenia in the frequencies of gene for COMT.Conclusion:①COMT genotype G/G associated with non-refractory schizophrenia in the Han nationality.And the results suggest COMT genotype G/G might be a protective gene to non-refractory schizophrenia.②COMT genes exerts no critical influence in positive family history schizophrenia and negative family history schizophrenia,positive schizophrenia and negative schizophrenia.PartⅡ:Associating study of 5-HT2A gene polymorphism and refractory schizophreniaObjective:①To compare the genetic polymorphisms of serotonin2A receptor(5-HT2A)between refractory and non- refractory schizophrenia in Han nationality.②To compare the genetic polymorphisms of 5-HT2A between positive family history schizophrenia and negative family history schizophrenia in Han nationality.③To compare the genetic polymorphisms of 5-HT2A between positive schizophrenia and negative schizophrenia in Han nationality.Method:92 refractory schizophrenia patients,91 non-refractory schizophrenia patients,63 positive family history schizophrenia,114 negative family history schizophrenia,116 positive schizophrenia,63 negative schizophrenia were recruited into the study.The gene polymorphism of 5-HT2A in all subjects was genotyped directly with polymerase chain reaction(PCR)and restriction fragment Length polymorphism(RFLP)technique,and to compare the differences of 5-HT2A polymorphism between refractory and non-refractory schizophrenia,positive family history schizophrenia and negative family history schizophrenia, positive schizophrenia and negative schizophrenia.Results:There were no significant differences in the frequencies of gene for 5-HT2A between refractory and non-refractory schizophrenia, positive family history schizophrenia and negative family history schizophrenia,positive schizophrenia and negative schizophrenia.Conclusion:5-HT2A genes exerts no critical influence in refractory schizophrenia and non-refractory schizophrenia,positive family history schizophrenia and negative family history schizophrenia,positive schizophrenia and negative schizophrenia.PartⅢ:Associating study of ApoE gene polymorphism and refractory schizophreniaObjective:①To compare the genetic polymorphisms of apoprotein lipase(ApoE)between schizophrenics and nomal subjects in Han nationality.②To compare the genetic polymorphisms of apoprotein lipase(ApoE) between refractory and non- refractory schizophrenia in Han nationality.③To compare the genetic polymorphisms of apoprotein lipase(ApoE) between positive family history schizophrenia and negative family history schizophrenia in Han nationality.④To compare the genetic polymorphisms of apoprotein lipase(ApoE)between positive schizophrenia and negative schizophrenia in Han nationality.Method:75 nomal subjects,138 refractory schizophrenia patients,97 non-refractory schizophrenia patients,61 positive family history schizophrenia,110 negative family history schizophrenia,149 positive schizophrenia,86 negative schizophrenia were recruited into the study.The gene polymorphism of ApoE in all subjects was genotyped directly with polymerase chain reaction(PCR)and restriction fragment Length polymorphism(RFLP)technique,and to compare the differences of ApoE polymorphism between schizophrenia and nomal subjects,refractory and non-refractory schizophrenia,positive family history schizophrenia and negative family history schizophrenia,positive schizophrenia and negative schizophrenia.Results:①The frequencies of ApoE genotype 3/4 and allele 4 in schizophrenia group(39.6%,21.9%)were significantly more prevalent than that in control group(6.7%,3.3%),while the frequency of ApoE gene2/3, gene 3/3 and allele 3 in schizophrenia group(0.0%,48.5%,72.3%)were lower than that in control group(1.3%,78.7%,88.7%).②The frequencies of ApoE genotype 3/4 and allele 4 in refractory schizophrenia group(46.4%, 26.1%)were significantly more prevalent than that in non-refractory schizophrenia group(29.9%,16%),while the frequency of ApoE gene 2/3 in refractory schizophrenia group(4.3%)were lower than that in non-refractory schizophrenia group(13.4%).③The frequencies of ApoE allele 4 in positive family history schizophrenia group(21.3%)were significantly more prevalent than that in negative family history schizophrenia group(10.9%),while the frequency of ApoE allele 3 and genotype 3/3 in positive family history schizophrenia group(70.5%,49.5%) were lower than that in negative family history schizophrenia group(83.2,%,70.0%).④There were no significant differences between positive schizophrenia and negative schizophrenia in the frequencies of gene for ApoE.Conclusion:①ApoE's allele 4 and gene 3/4 may play an important role in schizophrenia and refractory schizophrenia.②Allele 4 of ApoE may be susceptible factor for positive family history schizophrenia,Allele 3 and genotype 3/3 of ApoE may be protect factor for negative family history.③ApoE genes exerts no critical influence in positive schizophrenia and negative schizophrenia.PartⅣ:Associating study of CYP2D6 gene polymorphism and refractory in schizophreniaObjective:①To compare the genetic polymorphisms of cytochrome P4502D6(CYP2D6)between refractory and non- refractory schizophrenia in Han nationality.②To compare the genetic polymorphisms of cytochrome P4502D6(CYP2D6)between positive family history schizophrenia and negative family history schizophrenia in Han nationality.Method:92 refractory schizophrenia patients,92 non-refractory schizophrenia patients,61 positive family history schizophrenia,123 negative family history schizophrenia were recruited into the study.The gene polymorphism of CYP2D6 in all subjects was genotyped directly with polymerase chain reaction(PCR)and restriction fragment Length polymorphism(RFLP)technique,and to compare the differences of CYP2D6 polymorphism between refractory and non-refractory schizophrenia,positive family history schizophrenia and negative family history schizophrenia.Results:①The frequencies of CYP2D6C188T genotype C/T(OR= 0.47,P=0.043)and allele C(OR=0.50,P=0.002)in refractory schizophrenia group were significantly lower than those in non-refractory schizophrenia group,while genotype T/T(OR=1.94,P=0.032)and allele T(OR=2.00,P=0.002)were more prevalent in refractory schizophrenia group.②There were no significant differences between positive family history schizophrenia and negative family history schizophrenia in the frequencies of gene for CYP2D6.Conclusion:①Our results indicate that CYP2D6C188T polymorphism associated with refractory schizophrenia in the Han nationality.And the results suggest that there might be a susceptibility gene to refractory schizophrenia on chromosome22(22q 13.1).②CYP2D6 genes exerts no critical influence in positive family history schizophrenia and negative family history schizophrenia. PartⅤ:A synthetical analysis on factors affecting the therapeutic effect of schizophreniaObjective:To explore the key factors affecting refractory schizophrenia.Method:Refractory Schizophrenia and non- refractory Schizophrenia patients were evaluated at ration by 9 clinical indexes,such as COMT, 5-HT2A,CYP2D6,COMT~* 5-HT2A,COMT~*CYP2D6,5-HT2A~* CYP2D,COMT~*5-HT2A~*CYP2D6 genetic polymorphisms,family history,positiv/negative symptom.The data were analysis with Logistic model andχ~2 test.Results:①Negative symptom was significantly associated with refractory schizophrenia,But COMT,5-HT2A and ApoE genes exerts no critical influence in positive and negative schizophrenia.②There was no significantly association between positive family history and COMT, 5-HT2A,CYP2D6 genetic polymorphisms of schizophrenia,So no significantly association was found between positive family history and refractory schizophrenia.But Allele 4 of ApoE may be susceptible factor for schizophrenics with positive family history,Allele 3 and genotype 3/3 of ApoE may be protective factor for negative family history.③Genotype 3/3 and allele 4 of ApoE,Genotype T/T and allele T of CYP2D6 associated with refractory schizophrenia,And they might be a susceptibility gene to refractory schizophrenia;COMT genotype G/G,ApoE genotype 2/3,CYP2D6 genotype C/T and allele C might be a protective gene to non-refractory schizophrenia.5-HT2A gene exerts no influence on the therapeutic effect of schizophrenia as a independent variable.④Through multivate data analysis,The key factors affecting the therapeutic effect of schizophrenia are positiv/negative symptom,COMT~* 5-HT2A,COMT and CYP2D6 genetic polymorphisms.Positive/negative symptom are the most important factors affecting the therapeutic effect of schizophrenia,while COMT~* 5-HT2A,COMT and CYP2D6 genetic polymorphisms are mainly forecast indexes,and there were interaction between COMT and 5-HT2A gene.Conclusion:The key factors affecting the therapeutic effect of schizophrenia are positiv/negative symptom,COMT~*5-HT2A,COMT and CYP2D6 genetic polymorphisms.