Association, Expression Studies And Meta-Analysis Of Genetic Variations Implicated In Schizophrenia

Schizophrenia (MIM 181500) is one of the most severe psychiatric disorders, with a worldwide incidence of 1%. Data from twin, family, and adoption studies provide strong evidence that schizophrenia is predominantly a genetic disorder with high heritability. However, the genes evoking schizophrenia remain unclear.Convergent evidence has suggested that oxidative stress and free radicals may be involved in the pathophysiology of schizophrenia. Glutamate-cysteine ligase, modifier subunit (GCLM) provides a significant protective mechanism against oxidative stress. The purposes of the current study were to determine the role of genetic variations and expression levels of GCLM in susceptibility to schizophrenia in the Chinese population. We conducted a case-control association study on GCLM involving 797 Chinese subjects and three tag-SNPs using directly sequencing. An expression study using quantitative real-time polymerase chain reaction (RT-PCR) was also carried out in a subgroup of 180 samples using peripheral blood leukocytes. No significant difference was detected in the association study for any of the three SNPs or haplotypes. The expression of GCLM was significantly lower in the clozapine-treated schizophrenia patients compared to the control group (P=0.0018) and higher in the chlorpromazine-treated subgroup compared to the control group (P=0.0259). The expression levels varied greatly with respect to drug-treatment, suggesting that GCLM may be one of the drug targets, further reminding me that variants in the gene locus may be responsible for a certain therapy. The association analysis did not support the theory that GCLM was related to schizophrenia in the Chinese Han population. However, we could not exclude the role of oxidative stress and GSH-related gene in the pathology and etiology of schizophrenia, and antipsychotics-treatment should be taken into consideration in the further investigation of such genes.2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP), one of the most promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. Our study aims to investigate the relationship between CNP and schizophrenia in the Chinese population and the effect of other factors on the expression level of CNP in schizophrenia. Five CNP SNPs were investigated in a Chinese Han schizophrenia case-control sample (n=180). The results were included in a meta-analysis. RT-PCR was conducted to examine CNP expression levels in peripheral blood lymphocytes. Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the CNP gene in schizophrenia. Our meta-analysis yields no positive evidence. The results suggest that the CNP gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population.