| Objectives The aim of this study is to estimate the association between genetic polymorphisms of tyrosine metabolic pathway genes(ADH1B,ALDH1A3,COMT,DBH,MAOA,TH)and the susceptibility to schizophrenia in Guangxi Zhuang people and Han people,layed the foundation of the genetic mechanisms of schizophrenia in Guangxi Zhuang people and Han people.Methods A case control study was performed.The schizophrenia patients were diagnosed according to ICD-10 criteria(The International Classification of Disease,tenth revision).The subjects in the association analysis were 700 unrelated schizophrenia patients(300 Zhuang and 400 Han)and 700 unrelated healthy controls(300 Zhuang and 400 Han).A Sequenom MassARRAY genotyping method was carried out to analysis 13 Single Nucleotide Polymorphism,SNPs(ADH1B gene variant rs1042026 and rs 17033,ALDH1A3 gene variant rs3809523 and rs1130738,COMT gene variant rs4633,rs4680and rs8185002,DBH gene variant rs1611114and rs5320,MAOA gene variant rs3027407 and rs5953210,TH gene variant rs6356 and rs7115640).Statistical analyses were carried out with SPSS 13.0 for windows,SHEsis,STAT11.0,GMDR 0.9 and R package.Result1.The analytic results of single nucleotide polymorphism associated with schizophrenia(1)Before bonferroni’s correction① Zhuang peopleFour SNPs were statistically significant associated with schizophrenia in Zhuang people.There were ADH1B gene variant rs1042026(GA vs.GG,OR=0.666,95%CI=0.467-0.950,P=0.025;AA +GA vs.GG,OR=0.666,95%CI=0.467-0.950,P=0.025),COMT gene variant rs4633(TT vs.CT,OR=0.721,95%CI=0.520-0.998,P=0.049),DBH gene variant rs1611114(TC vs.CC,OR=0.627,95%CI=0.431-0.912,P=0.015),TH gene variant rs6356(GA + AA vs.GG,OR=2.791,95%CI=1.074-7.254,P=0.035).The other SNPs were not statistically significant associated with schizophrenia in Zhuang people(P>0.050).②Han peopleTwo SNPs were statistically significant associated with schizophrenia in Han people.There were MAOA gene variant rs3027407(AG vs.AA,OR=0.607,95%CI=0.392-0.941,P=0.025)and rs5953210(AG vs.GG,OR=0.464,95%CI=0.296-0.728,P=0.001;AA + AG vs.GG,OR=0.746,95%CI=0.562-0.991,P=0.043).The other SNPs were not statistically significant associated with schizophrenia in Han people(P>0.050).③The combination populationFour SNPs were statistically significant associated with schizophrenia in the combination population.There were ADH1B gene variant rs1042026(GA vs.GG,OR=0.791,95%CI=0.629-0.994,P=0.045;),COMT gene variant rs4633(T vs.C,OR=0.836,95%CI=0.705-0.992,P=0.040)and rs4680(AA + GA vs.GG,OR=0.785,95%CI=0.635-0.971,P=0.026),TH gene variant rs6356(GG vs.AA,OR=1.911,95%CI=1.008-3.623,P=0.047;GG vs.GA + AA,OR=1.907,95%CI=1.010-3.600,P=0.047).The other SNPs were not statistically significant associated with schizophrenia in combination population(P>0.050).(2)After bonferroni’s correctionExcept for MAOA gene variant rs5953210(P<0.004)wasstatistically significant associated with schizophrenia in Han people,all SNPs were not statistically significant associated with schizophrenia after Bonfermni’s adjustment(P>0.004).Compared with MAOA gene variant rs5953210 GG carriers,AG carriers can reduce the risk of schizophrenia in Han people significantly(OR=0.464,95%CI=0.296-0.728,P=0.001).2.The results of haplotype analysisThe A-A haplotype of ADH1B gene variant rs1042026 and rs17033 has a protective effect on schizophrenia in Zhuang samples(OR=0.668,95%CI=0.468-0.954,P=0.023,adjusted P was 0.025).The T-A-G haplotype can statistically significant reduce the risk of schizophrenia in Zhuang samples(OR=0.285,95%CI=0.0821-0.987,P=0.019,adjusted P was 0.015).The other haplotypes were not statistically significant associated with schizophrenia in Zhuang samples,Han samples and combined samples respectively(P>0.050).3.The results of gene-gene interaction analysisThe GMDR analysis suggested that DBH gene variant rs1611114,ALDH1A3 gene variant rs3809523 and COMT gene variant rs8185002 might cooperatively contribute to schizophrenia in Zhuang samples.Furthermore,logistic regression models suggested that rs1611114TC,rs3809523AQ rs8185002GT can cooperatively reduce the risk of schizophrenia in Zhuang samples significantly(OR=0.511,95%CI=0.282-0.9277,P=0.027)and the interaction of rs1611114TC,rs3809523AA,rs8185002GT has an edge protective effect on schizophrenia in Zhuang samples(OR=0.350,95%CI=0.122-1.000,P=0.050).MAOA gene variant rs5953210 and ALDH1A3 gene variant rs3 809523 might cooperatively contribute to schizophrenia in Han samples.However,logistic regression models did not found any positive results(P>0.050).In the combined samples,no gene-gene interactions were statistically significant associated with schizophrenia.Conclusion1.Compared with MAOA gene variant rs5953210 GG carriers,AG carriers can reduce the risk of schizophrenia in Han people significantly2.The A-A haplotype of ADH1B gene variant rs1042026 and rs17033 has a protective effect on schizophrenia in Zhuang samples.The T-A-G haplotype can statistically significant reduce the risk of schizophrenia in Zhuang samples.3.DBH gene variant rs1611114TC,ALDH1A3 gene variant rs3809523 AG,COMT gene variant rs8185002 GT can cooperatively reduce the risk of schizophrenia in Zhuang samples significantly and the interaction of rs 1611114 TC,rs3809523 AA,rs8185002 GT has an edge protective effect on schizophrenia in Zhuang samples. |
