Association Study Among Phosphatidase A2, Schizophrenia And Depression

Schizophrenia and depression are currently common mental disorders in China, with the highest prevalence and economic burden. Not only do diseases bring the patients lifelong agony, but also long-term burden to families and the society. The etiology research of schizophrenia and depression has been focus of mental disorders. This study, based on neural membrane phospholipids metabolism dysfunction hypothesis, and PLA2's important role in the pathogenesis of mental disorders, has discussed the relationship among PLA2 activity, PLA2 gene polymorphism, schizophrenia and depression. The results will provide clues to etiology for two kinds of mental disorders.ObjectiveTrying to discuss the relationship between PLA2 activity and the two mental disorders, also the relationship betweenPLA2G4C and PLA2G4B gene polymorphism and the two mental disorders, we use the first-episode schizophrenia and depression patients and healthy people as subjects, all of whom are Northern Han Chinese people, to explore the risk factors and the susceptibility gene locus.Methods①The patients were from the inpatients of Changchun No.6 hospital between March and September 2009, all of whom were firstly diagnosed as having a schizophrenia or depression 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 third edition(CCMD-3). A total of 102 schizophrenia patients and 100 depression patients were recruited.100 healthy control come from an enterprise of Changchun city.②Using the neutralization titration, we detected the serum PLA2 activity of schizophrenia, depression patients and healthy controls respectively. Usingχ2 test to analysis the circumstance of gender and age distribution in three groups, and one-way ANOVA to analysis the difference of PLA2 activity among three groups, besides we compare the PLA2 activity among subgroups according to age and gender③Genomic DNA used was extracted from the whole blood sample by a DNA extraction kit(Promega,USA). Using the PCR-RFLP to detect the polymorphism of rs1549637, located on PLA2G4C gene, and rs1648833 located on PLA2G4B gene. The Hardy–Weinberg equilibrium for genotypic distributions was tested byχ2 test, also did the alleles distribution. The distribution of genotype among groups was tested by exact probability.Results①To analysis the comparison of age and sex distribution among three groups, the results show that the distributions of age have no significant difference(χ2=5.398,P>0.05), neither did the distributions of gender(χ2=0.570,P>0.05).②Analyzing the serum PLA2 activity of three groups, we discover that the serum PLA2 activity have significant differences(F=481.55,P<0.001). Both the serum PLA2 activity of the schizophrenia and depression group are higher than that in control(P<0.01), but there was no difference of PLA2 activity between the two mental disorders(P=0.814).③According to the gender we analyze the serum PLA2 activity of subgroups, and the results showed that there were significant differences of males(F=182.57,P<0.001) among three groups, so did that of females(F=304.91,P<0.001).Whatever the gender is, the mental-disorder patients'PLA2 activity was higher than that of healthy control. But there were no differences of PLA2 activity between the males (P=0.501) of schizophrenia or depression, neither did that of females (P=0.458).④According to the age of subject, we divided them into 4 subgroups: below 30, between 30 and 39, between 40 and 49, and over 50. The results of PLA2 activity analysis showed that there were significant differences among three groups in all of the age subgroups. The mental-disorder patients'PLA2 activity was higher than that of control, but there were no differences between schizophrenia and depression in all of the 4 age subgroups.⑤The comparison of schizophrenia patients'PLA2 activity showed that there was no difference(F=1.294,P>0.05)among 4 age subgroups. None did that of depression patients(F=0.844,P>0.05) and healthy control(F=1.443,P>0.05).⑥The Hardy–Weinberg equilibrium for the 2 genotypic distributions were tested by using the chi-square(χ2)goodness-of-fit test. The goodness-of-fit test showed that the genotypic distributions of rs1549637 and rs1648833 were all in Hardy-Weinberg equilibrium in the three groups (P>0.05).⑦There were no significant differences for the frequencies of genotype and alleles of rs1549637 at PLA2G4C locus among three groups (P>0.05).⑧There were no significant differences for the frequencies of genotype and alleles of rs1648833 at PLA2G4B locus among three groups (P>0.05).⑨The comparison of PLA2 activity between homozygous and mutation genotypes of rs1549637 in schizophrenia group, showed that there were no differences between the two types. None did that of depression group or healthy control. Meanwhile, the comparison of PLA2 activity between homozygous and mutation genotypes of rs1648833, showed that there were no differences between the two types in the three groups respectively.Conclusions①There is an association among the increased serum PLA2 activity , schizophrenia and depression. There are no differences of PLA2 activity between schizophrenia and depression patients. The same results are also found in subgroup analysis according to the age and gender.②There are no genetic associations among the PLA2G4C (rs1549637) locus, schizophrenia and depression; neither did the PLA2G4B (rs1648833).The frequencies of homozygous and mutation genotypes of the two locus reveal no associations with schizophrenia or depression.③The comparison of PLA2 activity between homozygous and mutation genotypes of the two locus showed that there were no differences between the two types in the three groups respectively.