Gen metilasyon durumlarının şizofreniye etkisi

Schizophrenia is a neuropsychiatric disorder caused by disease in brain development in which genetic and environmental factors play a role. Despite neurobiological, clinical and genetic studies, the interactions and pathogenic mechanisms of the two main etiological factors are not fully understood. Although genetic factors alone have an important effect on the development of the disease, the presence of environmental factors on the genes that play a role in schizophrenia may explain the risk factors of the disease. Therefore, studies have focused on the effects of genetic and environmental factors on the development of schizophrenia. As environmental factors can cause changes in gene expression through epigenetic mechanisms, it is thought to alter gene expression networks involved in neuronal regulation. Genes are epigenetically activated or silenced in response to environmental factors during or after gametogenesis and embryogenesis. In general, methylation of 5'cytosine in the DNA sequence on gene promoters prevents binding of transcription factors and reduces gene expression. Studies conducted in this direction confirm the results of both postmortem human brain and peripheral blood samples examining changes in DNA methylation in candidate gene promoters. For this purpose, differences in DNA methylation pattern of Matrix metalloproteinase-9 (MMP-9), which has recently been associated with glutamate regulation and contribute to pathological synaptic plasticity in schizophrenia, were investigated. Pyro-sequencing method was used to determine DNA methylation of MMP-9 at positions CpG7-1, CpG7-2, CpG7-3, CpG7-4, CpG7-5 in peripheral blood cells from 40 schizophrenic patients and 32 healthy samples. MMP-9 methylation changes were compared with the mean MMP-9 methylation of healthy subjects. Significant differences were found in the position of CpG7-3, CpG7-4, CpG7-5 and the mean methylation pattern.