Analysis of COMT Val158Met polymorphisms and methylation in Chinese male schizophrenia patients with homicidal behavior

Schizophrenia is a severe mental disorder, and its mechanisms have not been fully elucidated. A functional single nucleotide polymorphism (SNP) present in the catechol-O-methyltransferase (COMT) gene, Val158Met (rs4680) (Chr22: 19,963,498), is possibly related to the violent behavior of schizophrenia patients. However, the specific variant that causes violent behavior is still unknown. Since the Val variation of Val158Met (rs4680) introduces a CG site into the sequence, the methylation level of the Val158Met (rs4680) region may also have an association with the homicidal behavior of schizophrenia patients. A case-control study was conducted that included 100 normal males, 100 schizophrenia inpatients, and 100 schizophrenia inpatients with homicidal behavior. A polymorphism of Val158Met (rs4680) and the methylation levels were analyzed by pyrosequencing. Compared to Met carriers, the Val/Val genotype was significantly associated with the homicidal behavior of schizophrenia patients. In addition, the methylation levels of the Val158Met (rs4680) region were significantly different between the three groups. Moreover, the methylation level of an rs4680-related CpG site was significantly associated with the Val/Val genotype which may contribute to the homicidal behavior of schizophrenia patients. In this study, we showed that the Val allele at Val158Met (rs4680) may be associated with the homicidal behavior of schizophrenia patients as well as that the methylation level of Val158Met (rs4680) could be affected by the variation of Val158Met (rs4680) and eventually contribute to the violent behavior of schizophrenia patients.