The Association Study Of Polymorphisms In CHRNA7 And COMT Gene With Sensory Gating Of First-episode Schizophrenia

ObjectiveThe genetic factor plays an important role in the etiology and pathogenesy of schizophrenia. Endophenotype study has afforded important strategy from new point of view to schizophrenia research. Startle reflex prepulse inhibition (PPI) and auditory evoked potential (P50) are two endophenotypes of schizophrenia, numerous evidences indicate that P50 of schizophrenia is very intimate to CHRNA7 gene, and so as PPI of schizophrenia to COMT gene. The objective of this study was to explore the association of P50 and PPI of schizophrenia with polymorphisms in CHRNA7 gene and COMT gene.MethodsSubjects140 first episode schizophrenia (Sch group), 100 normal controls (Control group) were involved in this study. Sch group met the diagnostic criterion of Schizophrenia or schizoid disorder, without antipsychotic drug treatment or drug treatment within 3 days. Organic diseases of brain and mental disorders associated with physical diseases and substance dependence has been excluded, no hearing impairment (subjective hearing threshold<40dB).Laboratory proceduresSch group were completed with the P50 and PPI testing after their admission. All subjects were extracted with their genome DNA. 3 SNPs (rs2337980, rs1909884 and rs883473) in CHRNA7 gene and 3 SNPs (rs4680, rs737865 and rs165599) in COMT gene were selected to be genotyped with polyacrylamide gel microarray techniques.Statistical methodsThe SPSS 13.0 statistical package was adopted to process the data, including Chi-square test to allele and genotype frequencies, t-test or Mann-Whitney U test to comparison of P50 and PPI indexes between wild-type group and mutation group. Unphased program was used to analyze inside group genotype frequencies of the SNPs. Results1 Hardy-Weinberg equilibrium testThe genotype frequencies of the 6 SNPs were not deviated from the Hardy-weinberg equilibrium (P>0.05) in all subjects, illustrating that the samples come from natural population of random mating.2 Association between schizophrenia and CHRNA7 geneThe data analysis showed statistical significance in the wild-type (TT) genotype distribution of rs2337980 between Sch group and control group (P<0.05), the former was fewer than the latter. Statistical significance was also found in the mutant (GG) genotype between Sch group and control group (P<0.05), the latter was more than the former.3 CHRNA7 gene and P50 of schizophreniaComparison of P50 index showed no statistical difference between wild-type group and mutation group of every SNP in CHRNA7 gene (P>0.05). No significance was found in comparison of genotype frequencies of SNPs in CHRNA7 gene between P50 abnormal group and P50 normal group (P>0.05).4 COMT gene and P50 of schizophreniaComparison of P50 index between wild-type group and mutation group of rs4680 in COMT gene showed significant statistical difference in S2 amplitude (P<0.01), the former's amplitude was higher than the latter's. Statistical difference was presented in S1 amplitude of rs737865 between the two groups (P<0.05), the former's amplitude was lower than the latter's, and no significance was found in rs165599 (P>0.05).5 COMT and PPI of schizophreniaComparison of PPI index in COMT gene exhibited statistical difference in PL of rs4680 between wild-type group and mutation group (P<0.05), the former was longer than the latter. Statistical difference was presented in the suppression ratio between the two groups of rs165599 (P<0.05), the former was lower than the latter. No significance was found in rs737865 (P>0.05).Conclusion 1 In the population of Yuedong region of China, the polymorphisms of rs2337980 and rs883473 in CHRNA7 gene may be associated with schizophrenia. The TT genotype of rs2337980 may be a protective genotype of schizophrenia, while the GG genotype of rs883473 might be act as a pathogenic genotype.2 In this study, no association is observed between the three SNPs (rs2337980, rs883473, rs1909884) of CHRNA7 gene and P50/PPI in schizophrenia. But there might be some linkages between the three SNPs (rs4680, rs737865, rs165599) of COMT gene and P50/ PPI in schizophrenia.3 In our study, the six SNPs of CHRNA7 gene and COMT gene present no genotype distribution significance or significance of mutation effect in schizophrenia patients having P50 and PPI impairment or not. The three SNPs of COMT gene relate to elevated sensory gating, DA level of prefrontal cortex perhaps influences modulating of sensory gating.