Methylenetetrahydrofolate dehydrogenase-1 (MTHFD1) 1958 G>A genetic polymorphism (rs2236225) is associated with lower schizophrenia risk: Preliminary study

Abstract

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the methylenetetrahydrofolate dehydrogenase-1 (MTHFD1) 1958 G>A polymorphism in this disorder is still poorly understood. The aim of this study was to assess the distribution of MTHFD1 1958 G>A allele and genotype frequencies in patients with schizophrenia and healthy controls. Also, we aimed to study the association of allele/genotype carriage of this single nucleotide polymorphism (SNP) with biochemical markers of the one-carbon metabolism (OCM) and with the severity of schizophrenia symptoms. Methods: The carriage of MTHFD1 1958 G>A alleles/genotypes were evaluated in 116 patients with schizophrenia and 62 healthy volunteers. Biochemical markers of OCM were studied in 89 patients and 59 volunteers. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG/AA: χ2 = 5.34; p = 0.021). A higher level of cobalamin in carriers of the wild GG genotype may indicate competitive inhibition of methylation processes in carriers of this genotype, which requires further study.