Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms

Version 1 : Received: 2 November 2021 / Approved: 5 November 2021 / Online: 5 November 2021 (12:51:14 CET)

How to cite: Zhilyaeva, T.; Chekanina, O.; Rukavishnikov, G.; Blagonravova, A.; Mazo, G.E. MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms. Preprints 2021, 2021110121 (doi: 10.20944/preprints202111.0121.v1). Zhilyaeva, T.; Chekanina, O.; Rukavishnikov, G.; Blagonravova, A.; Mazo, G.E. MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms. Preprints 2021, 2021110121 (doi: 10.20944/preprints202111.0121.v1).

Abstract

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Keywords

schizophrenia; MTHFD1 1958 G> A; folate metabolism; methylation; tetrahydrobiopterin

Subject

MEDICINE & PHARMACOLOGY, Psychiatry & Mental Health studies

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