Association Study Between Schizophrenia And Serum Phosphatidase Activity,PLA2G4C Gene Polymorphism

Schizophrenia is the most common and serious mental illness. It is the 21th Century difficulties of medical study. The difficulties of pathogenic can not use the single factor of biological, environmental and psychological factors to explain. In recent years, with the development of molecular biology technology, the study about schizophrenic genetics has got the great progress, proposed the many etiopathogenisis hypothesis, until now, the hypothesis of nerve membrane metabolism dysfunction is one of most popular hypothesis.Objectives,Using the method of bioinformatics, biochemical and molecular genetics, we want to discuss the relationship between schizophrenia and serum PLA2 activity and PLA2G4C gene polymorphism, try to discover the predisposing genes and molecular genetics of schizophrenia.Methods,(1) The detection of serum PLA2 activityA total of 115 Chinese schizophrenic, consisting of 48 males and 67 females, were recruited for the activity detection. These subjects originally came from Changchun mental health hospital. The patients were firstly admitted to the psychiatric hospital during the period between March and September in 2006.They were diagnosed as having a schizophrenic illness using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and Chinese classification and diagnostic criteria of mental disorders, the second revised edition (CCMD-II-R).Healthy control comes from Changchun blood bank, consisting of 41 males and 74 females. The selected control members are matched with case members by gender and age, no individual and family mental illness history, having the same culture background and life eating habit. All the subjects are excluded the diseases which can influence the level of PLA2 activity. Under the status of all the subjects having the known the fact, taking the subjects the blood from peripheral vein (no anticogulation) 5 mL, abstract the serum,put them in to -40℃deep-freeze.Using the neutralization titration, we respectively detect the serum PLA2 activity of case and control. Usingχ2 test to analysis the circumstance of sex distribution in two groups; age distribution and serum PLA2 activity comparison use the independent sample t test; Using the t test andχ2 test to analysis the relationship between the serum PAL2 activity of different sex, medical history, clinical symptom, birth season and premorbid personality in case and schizophrenia.(2) The detection of PLA2G4C gene polymorphismA total of 803 Chinese Han descent subjects, consisting of schizophrenic 403 and 400 healthy control, were recruited for the genetic analysis. These subjects originally came from Siping and Kaixuan psychiatric hospital. The patients (216 males and 187 females) were admitted to a psychiatric hospital during the period between 2000 and 2005. They were diagnosed as having a schizophrenic illness using ICD-10 and CCMD-II-R). The healthy control is coming from Changchun blood bank, consisting of 284 males and 116 females.The diagnosis was made independently by at least two psychiatrists. All the subjects gave written informed consent for the genetic analysis and taken blood from peripheral vein. Genomic DNA used for PCR amplification was extracted from the whole blood sample using a DNA extraction kit ( Promega, USA). Using the PCR-LDR to detect the polymorphism of rs1549637,which located on the PLA2G4C gene. The Hardy–Weinberg equilibrium for genotypic distributions was tested using the chi-square (χ2) goodness-of-fit test; The relationship between schizophrenic clinical symptom, birth season, premorbid personality, clinical history and the SNP was tested by theχ2 test.Results,(1) The detection of serum PLA2 activity①The analyses results of epidemiological surveyThe results indicate that first age of onset of schizophrenia was between 13 and 61 years old, the mean of age of onset was 21.72±5.109 years old. Most cases onset at 10～30 years old. There were no difference between male and female schizophrenic with fist age of onset, birth season and clinical history (t = 0.436,P=0.663;χ2=2.340,P=0.139;χ2=2.900,P=0.090). But the premorbid personality has the sex difference(χ2=7.400,P=0.020),most is introversion. Only the distribution of delusion of jealousy has significant difference at male cases and female cases in all the clinical symptoms (P<0.05), the incidence of delusion of jealousy in female case was higher than in male cases, other negative and positive symptoms have no significant difference in male and female cases.②The results of experimentTo analysis the comparison of age and sex distribution between case and control, the results show that the distribution of age has no significant difference(t=1.360, P>0.05),the distribution of sex also has no significant difference(χ2 = 1.780, P>0.05),according with the needs of design. We analysis the serum PLA2 activity of two groups, discover that the serum PLA2 activity in case is higher than the serum PLA2 activity in control ( P<0.001).There was no significant sex difference between two groups(P>0.05). The serum PLA2 activity of schizophrenic different personality subgroups also has no gender difference(P>0.05).According to different age subgroups, 10～and above 61 age group, there were no significant difference of distribution of serum phospholipase A2 activity in both cases and controls(p>0.05),other four groups that age between 21～,31～,41～,51～age group, there were significant difference in distribution of serum phospholipase A2 activity in both cases and controls(p﹤0.001).According to the different clinical symptoms and positive clinical history ,we put the case into propotional subtypes, the results show that the serum PLA2 activity of different subtypes has no significant difference.(2) The detection of PLA2G4C gene polymorphism①Hardy-Weinberg equilibrium testThe Hardy–Weinberg equilibrium for genotypic distributions was tested using the chi-square (χ2 ) goodness-of-fit test. The goodness-of-fit test showed that the genotypic distributions of rs1549637 were in Hardy-Weinberg equilibrium in both case and control ( P > 0.05).②The results of experimentThere was no significant difference for the frequencies of genetype and alleles of rs1549637 at PLA2G4C locus between the case and the control (P>0.05). This indicated no association between rs1549637 and schizophrenia. According to the gender subtype, the results indicate only the frequencies of genetype of rs1549637 at PLA2G4C locus has significant difference between the male case and male control (P<0.05), but the frequencies of genetype of rs1549637 at PLA2G4C locus has no significant difference between female case and female control (P>0.05), the frequencies of alleles of rs1549637 at PLA2G4C locus has no significant difference in both sex subgroups (P>0.05).We analysis the clinical symptoms subgroups of the cases, the results show that there were association among the frequencies of genetypes of rs1549637 locus and delusion of reference, delusion of grandeur and hallucination-delusion syndrome (P<0.05), and the frequencies of alleles of rs1549637 locus does not related with any clinical symptoms (P>0.05). The frequencies of genetype and alleles of rs1549637 at PLA2G4C locus have no relationship with positive family history, premorbid personality and birth season in case (P>0.05).Though the present study shows, rs1549637 locus has no relationship with schizophrenia, meantime the locus has correlation with many clinical symptoms, and we confirmed that schizophrenia has clinical heterogeneity and genetic heterogeneity.Conclusion,According to the above-mentioned analytic results, we can reach the following conclusions: There is relationship between the increased serum PLA2 activity with schizophrenia, has no relationship among the serum PLA2 activity and premorbid personality, positive family history, birth season, and clinical features; There is no genetic association between the PLA2G4C (rs1549637) locus and schizophrenia; but it associates with many schizophrenic clinical symptoms and male schizophrenic.In a word, these findings thoroughly suggest that PLA2 associate with schizophrenia, which support the metabolic disorder hypothesis of nerve cell membrane phospholipids powerfully, meantime we also confirm that Schizophrenia has the clinical and genetic heterogeneity. But because Phospholipase A2 gene families has many kinds of members, we should be done more researchs to find which kind of gene leads to schizophrenia.