Analysis of methylation and -141C Ins/Del polymorphisms of the dopamine receptor D2 gene in patients with schizophrenia

•The methylation rates of DRD2 were significantly lower in SCZ patients and were correlated with BPRS.•The -141C Ins/Del polymorphisms were associated with these methylation rates and DIEPSS.•Methylation rates and the -141C Ins/Del polymorphism of DRD2 may be useful biomarkers for SCZ. The gene for dopamine receptor D2 (DRD2) is associated with schizophrenia (SCZ). Epigenetic changes may be related to SCZ pathology. The -141C Ins/Del polymorphism in DRD2 (rs1799732) is functional and associated with SCZ. Fifty SCZ patients and 50 control subjects were newly recruited and analyzed in addition to 50 previously reported SCZ samples and 50 previously reported control samples. Genomic DNA from peripheral leukocytes was analyzed. We replicated analysis of DNA methylation rates at seven CpG sites (CpG 1-1 to 1-7) and also analyzed five additional sites (CpG 2-1 to 2-5) in the upstream region of DRD2. We also performed genotyping of -141C IIns/Del and analyzed the effects of -141C Ins/Del on methylation of DRD2. Methylation rates were significantly lower in SCZ patients compared to control subjects, respectively. In control subjects, the methylation rates were significantly lower in individuals with the Ins/Ins genotype than in Del allele carriers. We replicated hypomethylation of the DRD2 promoter region in SCZ patients compared to age-matched control subjects. The -141C Ins/Del polymorphism affected the methylation rates in regions of DRD2. Hypomethylation and the -141C Ins/Del polymorphism of DRD2 may be biomarkers for SCZ.