A Case-control Study Between Gene Polymorphisms Of Fatty Acids Metabolic Rate-limiting Enzymes And Paranoid Schizophrenia

Schizophrenia is a complex and serious genetic disorder, whose pathogenesis remains undefined. At present, it has been thought both multiple genes and environmental factors contribute to its etiology. Whether the nervous system functional activity is normal or not, it has a close relationship with schizophrenia. Lipid membrane hypothesis of schizophrenia provides new ideas for exploring the pathogenesis. The PUFA in the phospholipids of cell membranes may metabolize abnormally caused by the genes variation of metabolic rate-limiting enzyme, which leads to schizophrenia.ObjectiveTo investigate an association between the gene polymorphisms of PUFA metabolic rate-limiting enzymes and paranoid schizophrenia with molecular biology, bioinformatics and nutriology. The present study tried to reveal the susceptible genes for paranoid schizophrenia.MethodsThe present study has chosen 3 genes in the metabolic pathway of PUFA as the candidate susceptibility genes, FADS1, FADS2 and ELOVL2. Case samples are 100 paranoid schizophrenia patients and control samples are 95 healthy people, all of whom are the Han nationality in the north of China. All the subjects gave written informed consent for the genetic analysis and were taken blood from peripheral vein.Genomic DNA used for PCR amplification was extracted from the whole blood sample using a DNA extraction kit. Three SNPs(single nucleotide polymorphisms), rs174556, rs174617 and rs3756963, located in the three genes respectively were genotyped by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method. Genotypes data were analyzed by statistical software SPSS 13.0. The genotype frequency distributions of SNPs were tested by the goodness-of-fit chi-square test, so as to verify the Hardy-Weinberg equilibrium. The UNPHASED3.012 program was applied to analyze the association between haplotype and paranoid schizophrenia as well as trans-phase interaction between SNPs tested. The chi-square test was used to analyzing the association between allelic, genotypic frequency distributions of the SNPs and paranoid schizophrenia as well as its clinical symptoms.Results1. The analytic results of general informationThe average age of paranoid schizophrenia patients was 36.24±11.98 years old. 43 of 100 were males while 57 of 100 were female. The average age of control was 34.39±9.74 years old. 43 of 95 were males while 52 of 95 were female. The sex distribution and the average age of the case and control groups had no significant difference.2. Hardy-Weinberg equilibrium testThe genotypic distributions of the patients group and the control group were tested using the chi-square goodness-of-fit test. The results showed that the 3 SNPs conformed to the Hardy-Weinberg equilibrium (P>0.05).3. Association between the allele, genotype of SNPs and paranoid schizophrenia The allelic and genotypic frequency distributions of SNPs rs174556 in FADS1 gene and rs174617 in FADS2 gene showed no significant difference between the case group and the control group (P>0.05). The allelic and genotypic frequency distributions of SNP rs3756963 in ELOVL2 gene showed significant difference between the case group and the control group (P<0.05).The distribution proportion of allele T in the case group was higher than that in the control group. There was significant difference between the case group and the control group of the frequency distribution of genotype TT (P<0.05). 4. Haplotype analysisThe results showed that there wasn't significant difference between the case group and the control group of the frequency distribution of rs174556-rs174617 haplotype (P>0.05).5. The interaction between gene and geneWith genotype TT of rs3756963 in ELOVL2 gene a conditional marker, the analytic results showed that the interaction between the genotype TT and all the other genotypes had significant difference between the case group and the control group (P<0.05). The distribution proportion of the case group was higher than that in the control group. The conditional marker CT genotype of rs3756963 and CC genotype of rs174556 in FADS1 gene had significant difference between the case group and the control group (P<0.05). The distribution proportion of the control group was higher than that in the case group.6. Association between the allele, genotype of SNPs and clinical symptomsThe genotype and allele frequency distribution of rs174556 in FADS1 gene had no statistical significance in all the clinical symptoms. The genotype and allele frequency distributions of rs174617 in FADS2 gene were associated with delusion of jealousy and other delusion (P<0.05), its genotype frequency distribution was also associated with delusion of negation (P<0.05). The allele and genotype frequency distribution of rs3756963 in ELOVL2 gene was associated with aggressive behavior (P<0.05). The allele frequency distribution of rs3756963 was also associated with delusion of influence (P<0.05). All SNPs of the 3 genes had no association with the negative symptoms.ConclusionsAccording to the analytic results, we can reach the following conclusions:1. rs174556 in FADS1 gene was not associated with paranoid schizophrenia.2. rs174617 in FADS2 gene was not associated with paranoid schizophrenia, while its allele and genotype frequency distributions were associated with the delusion of jealousy and other delusion of paranoid schizophrenia. In addition, its genotype frequency distribution was associated with the delusion of negation.3. rs3756963 in ELOVL2 gene was associated with paranoid schizophrenia.4. The allele and genotype frequency distributions of rs3756963 in ELOVL2 gene were associated with aggressive behaviour of paranoid schizophrenia, while its allele frequency distribution was also associated with the delusion of influence.5. The haplotype system of rs174556- rs174617 was not associated with paranoid schizophrenia6. The distribution of TT genotype of rs3756963 in ELOVL2 gene was higher in the case group than that in the control group.The present study found that ELOVL2 gene was associated with paranoid schizophrenia, which supported the lipid membrane hypothesis of schizophrenia. The specific mechanism of this hypothesis is worth exploring.