Association Study Of GPx1,GSTM1,GSTT1 And GSTP1 Gene Polymorphisms With Schizophrenia In A Chinese Han Population

Objective: The glutathione peroxidase 1(GPx1)gene encodes GPx1,which is one of the antioxidant enzymes in the body.GPx1 is widely distributed in the body,mainly in the cytoplasm of cells,mitochondria,and peroxidase structures in some cells.Although there are a variety of antioxidant enzymes in the body that can help the body resist external oxides,many studies have found that GPx1 is more effective than catalase in removing intracellular peroxides.Several studies have confirmed that GPx1 may be involved in the pathophysiology of various diseases such as Alzheimer’s disease,depression,autism,and cerebral hemorrhage.The glutathione sulfur transferase M1,T1,and P1(glutathione Stransferase mu-1,theta-1,and pi-1)genes encode the GSTM1,GSTT1,and GSTP1 proteins,respectively.GSTM1,GSTT1,and GSTP1 are also one of the body’s main antioxidant enzymes,and are found in the body’s blood,cerebrospinal fluid,and other tissues.These three enzymes belong to the phase II biotransformation enzymes and are involved in the detoxification of various compounds in the body,including the detoxification of oxides produced by oxidative damage.Changes in the GSTs system may lead to incomplete removal of toxins from the body and excessive production of toxic products,which may lead to imbalance of the redox system,resulting in inflammation and cell damage.In many exploration studies on the biological causes of schizophrenia,scholars have found that there is peroxidation in patients with schizophrenia,and put forward the hypothesis of oxidative stress in schizophrenia.Reactive oxygen species(ROS)and reactive nitrogen species(RNS)and the long-term imbalance between the antioxidant system affect the function of the nervous system and eventually lead to the occurrence of schizophrenia.Increased peroxidation content will also cause amino acid modification errors,peptide bond breaks,and protein cross-linking into polymers.For the function of proteins,peroxidation also acts on polyunsaturated fatty acids on cell membranes and organelle membranes,or directly binds to receptors on cell membranes and organelle membranes,resulting in extensive cell damage and even apoptosis,affecting the function of the nervous system,leading The occurrence of psychiatric illness.It can be seen that the activities of GPx1,GSTM1,GSTT1 and GSTP1 are closely related to mental and neurological diseases.In recent years,with the deepening of molecular genetics research,scholars have not only studied the relationship between protein content and disease,but also the relationship between genes and disease.At present,in the research of GPx1 gene polymorphism and schizophrenia,most studies focus on exploring the correlation between GPx1 gene single nucleotide polymorphism(rs1050450 or Pro198leu)and schizophrenia,and for other sites of GPx1 gene Little exploration.At present,the relationship between the genetic polymorphisms of GSTM1,GSTT1 and GSTP1 and schizophrenia is also very limited,and the research on the genetic polymorphisms of GSTM1 and GSTT1 is limited to a small fragment.Therefore,this study uses a case-control method,using PCR and RFLP detection methods,for the GPx1(rs1800668 C / T,rs1050450 C / T),GSTM1(rs737497,rs1065411),GSTT1(rs4630,11550605),and GSTP1 of Chinese Han population.(rs1695A / G,rs4891 C / T)gene polymorphisms to determine the correlation between GPx1,GSTM1,GSTT1,and GSTP1 gene polymorphisms and schizophrenia.It is expected to add new evidence for genetic research in psychiatry.Methods: Research subjects: A total of 805 research subjects were included in this study.A total of 379 patients with schizophrenia aged 18 to 65 were included in the case group.All patients were inpatients from Liaoning Province,and there was no genetic relationship between different patients.This study included 426 healthy people aged 18 to 65 years to form a control group.The control group were all from the same Chinese region as the case group patients,and were healthy individuals without mental illness and severe physical illness.Experimental method: 2ml of peripheral venous blood was collected on the day of enrollment as the research sample of this study.We used DNA purification method,polymerase chain reaction and restriction fragment length polymorphism analysis method for GPx1(rs1800668 C / T,rs1050450 C / T),GSTM1(rs737497,rs1065411),GSTT1(rs4630,11550605)and GSTP1(rs1695A / G,rs4891 C / T)gene polymorphisms were determined.Statistical analysis: This study uses SPSS 22.0 software package to analyze experimental data.General demographic data and genotype analysis use chi-square test or Fisher’s exact value test;SHEsis software is used to perform linkage disequilibrium analysis and haplotype analysis on experimental data analysis.All data are expressed by frequency and percentage(%),and P < 0.05 indicates that the difference is statistically significant.Results: 1.The genotype and dominant model frequency of GPx1 rs1800668 C / T were different between the case group and the control group(P < 0.05).However,the allele type and recessive model frequency of GPx1 rs1800668 C / T were not different between the two groups(P > 0.05).The genotype,allele,dominant model and recessive model frequency of GPx1 rs1050450 C / T were not different between the case group and the control group(P > 0.05).GSTM1 gene polymorphisms had significant statistical differences between the case group and the control group(P < 0.05).The GSTT1 gene polymorphism did not show statistically significant differences between the case group and the control group(P > 0.05).The frequencies of GSTP1 rs1695 A / G and GSTP1 rs4891 T / C genotypes,alleles,dominant models,and recessive models were not significantly different between the case group and the control group(P > 0.05).2.In a study with different genders as subgroups,this study found that the genotype,allele,and dominant model frequencies of GPx1 rs1800668 C / T were different between the case group and the control group in the male population(P < 0.05),but there was no difference in the frequency of the recessive model between the male case group and the control group(P > 0.05).In the study of the female population,the genotype,allele,dominant model,and recessive model frequencies of GPx1 rs1800668 C / T were not significantly different between the case group and the control group(P > 0.05).In studies of GPx1 rs1050450 C / T of different genders,the results showed that there was no significant difference in the frequency of genotypes,alleles,dominant models,and recessive models between the case group and the control group,whether in men or women(P > 0.05).GSTM1 gene polymorphisms also had significant statistical differences in different gender case groups and control groups(P < 0.05).The GSTT1 gene polymorphism did not show statistically significant differences between the case group and the control group in both the male and female populations(P > 0.05).The frequencies of GSTP1 rs1695 A / G and GSTP1 rs4891 T / C,regardless of the genotype,allele,dominant model,or recessive model,were not significantly different between the case group and the control group(P > 0.05).3.The haplotype analysis results of GPx1 rs1800668 C / T and GPx1 rs1050450 C / T showed that there were differences in the four haplotypes of CC,CT,TC,and TT in the case group and the control group(P < 0.05).In the male group,the frequencies of the CC,CT,and TC haplotypes were significantly different between the case group and the control group(P <0.05),but the frequencies of the TT haplotype were not significantly different between the two groups(P > 0.05).In the female population,the frequencies of the four haplotypes of CC,CT,TC,and TT were different between the two groups(P < 0.05).The combined genotype results of GSTM1 and GSTT1 showed that only the GSTM1-/ GSTT1-genotype showed a statistically significant difference between the case group and the control group(P < 0.05),while GSTM1+ / GSTT1 +,GSTM1 + / GSTT1-,GSTM1-/ GSTT1+ genotype did not show a difference between the case group and the control group(P > 0.05),and this difference was also shown in people of different genders.Haplotype analysis of GSTP1 rs1695 A / G and rs4891 T / C showed that there were no significant differences in the frequencies of CA,CG,TA,and TG haplotypes between the case group and the control group(P > 0.05).The haplotype frequencies of GSTP1 rs1695 A / G and rs4891 T / C in the subgroup were also not significantly different between the case group and the control group(P > 0.05).Conclusions: 1.The C allele of rs1800668 C/T may be a protection factor for male schizophrenia.2.The GSTM1 null genotype of GSTM1 may be a risk factor for schizophrenia.3.The combined genotypes of GSTM1 and GSTT1 indicate that GSTM1-/ GSTT1-genotype may be a risk factor for schizophrenia.4.CT and TC(GPx1 rs1800668 C/T and rs1050450 C/T)haplotypes may be susceptible to schizophrenia in the population.5.GPx1,GSTM1 and GSTT1 gene polymorphism are associated with schizophrenia in the Han population in northern China.