Objective. To study the association of the C677T polymorphism of the MTHFR gene with the risk of developing schizophrenia in a large cohort including patients with schizophrenia and mentally healthy people and to investigate the association of this polymorphism with the severity of schizophrenia symptoms and the simultaneous effects of genetic variants and environmental factors on these symptoms. Materials and methods. The genotyping cohort consisted of 1357 schizophrenia patients and 711 controls. Symptom severity was evaluated on the PANSS. Environmental factors were birth complications and history of traumatic brain injury. Results and conclusions. No association was found between the C677T polymorphism of the MTHFR gene and schizophrenia. There was no genotype effect on symptom severity on PANSS subscales. The interaction between the polymorphism of interest and environmental factors had no effect on the severity of schizophrenia symptoms. These results do not support data from a number of investigations of an association between the C677T polymorphism of the MTHF gene and schizophrenia
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G. Boog, “ Obstetrical complications and subsequent schizophrenia in adolescent and young adult offsprings: is there a relationship?” J. Gynecol. Obstet. Biol. Reprod., 114, No. 2, 130–136 (2004), https://doi.org/https://doi.org/10.1016/j.ejogrb.2003.09.041.
S. Lukkari, H. Hakko, A. Herva, et al., “Exposure to obstetric complications in relation to subsequent psychiatric disorders of adolescent inpatients: specific focus on gender differences,” Psychopathology, 45, No. 5, 317–326 (2012), https://doi.org/https://doi.org/10.1159/000336073.
M. Buoli, V. Bertino, A. Caldiroli, et al., “Are obstetrical complications really involved in the etiology and course of schizophrenia and mood disorders?” Psychiatry Res., 241, 297–301 (2016), https://doi.org/https://doi.org/10.1016/j.psychres.2016.05.014.
L. Wan, Y. Li, Z. Zhang, et al., “Methylenetetrahydrofolate reductase and psychiatric diseases,” Transl. Psychiatry, 8, No. 1, 242 (2018), https://doi.org/https://doi.org/10.1038/s41398-018-0276-6.
J. W. Muntjewerff, M. L. Hoogendoorn, R. S. Kahn, et al., “Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study,” Am J. Med. Genet. B. Neuropsychiatr. Genet., 135B, No. 1, 69–72 (2005), https://doi.org/https://doi.org/10.1002/ajmg.b.30179.
T. V. Zhilyaeva, A. V. Sergeeva, A. S. Blagonravova, et al., “Association study of methylenetetrahydrofolate reductase genetic polymorphism 677C>T with schizophrenia in hospitalized patients in population of European Russia,” Asian J. Psychiatr., 32, 29–33 (2018), https://doi.org/https://doi.org/10.1016/j.ajp.2017.11.027.
S. Numata, M. Kinoshita, A. Tajima, et al., “Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis,” BMC Med. Genet., 16, 54 (2015), https://doi.org/https://doi.org/10.1186/s12881-015-0197-7.
N. C. Allen, S. Bagade, M. B. McQueen, et al., “Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database,” Nat. Genet., 40, No. 7, 827–834 (2008), https://doi.org/https://doi.org/10.1038/ng.171.
J. W. Muntjewerff, R. S. Kahn, H. J. Blom, and M. den Heijer, “Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis,” Mol. Psychiatry, 11, No. 2, 143–149 (2006), https://doi.org/https://doi.org/10.1038/sj.mp.4001746.
M. Kinoshita, S. Numata, A. Tajima, et al., “Cumulative effect of the plasma total homocysteine-related genetic variants on schizophrenia risk,” Psychiatry Res., 246, 833–837 (2016), https://doi.org/https://doi.org/10.1016/j.psychres.2016.10.017.
E. T. Betcheva, T. Mushiroda, A. Takahashi, et al., “Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population,” J. Hum. Genet., 54, No. 2, 98–107 (2009), https://doi.org/https://doi.org/10.1038/jhg.2008.14.
R. Philibert, T. Gunter, N. Hollenbeck, et al., “No association of the C677T methylenetetrahydrofolate reductase polymorphism with schizophrenia,” Psychiatr. Genet., 16, No. 5, 221–223 (2006), https://doi.org/https://doi.org/10.1097/01.ypg.0000242192.28526.fa.
E. G. Jönsson, K. Larsson, M. Vares, et al., “Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study,” Am J. Med. Genet. B. Neuropsychiatr. Genet., 147, No. 6, 976–982 (2008), https://doi.org/https://doi.org/10.1002/ajmg.b.30671.
1000 Genomes Project, www.internationalgenome.org.
A. Yoshimi, B. Aleksic, Y. Kawamura, et al., “Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data,” Schizophr. Res., 124, No. 1–3, 216–222 (2010), https://doi.org/https://doi.org/10.1016/j.schres.2010.07.011.
B. Lajin, A. Alhaj Sakur, R. Michati, and A. Alachkar, “Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort,” Asian J. Psychiatr., 5, No. 2, 144–149 (2012), https://doi.org/https://doi.org/10.1016/j.ajp.2012.03.002.
M. Hill, K. Shannahan, S. Jasinski, et al., “Folate supplementation in schizophrenia: a possible role for MTHFR genotype,” Schizophr. Res., 127, No. 1–3, 41–45 (2011), https://doi.org/https://doi.org/10.1016/j.schres.2010.12.006.
J. W. Muntjewerff, H. Gellekink, M. den Heijer, et al., “Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia,” Eur Neuropsychopharmacol., 18, No. 2, 99–106 (2008), https://doi.org/https://doi.org/10.1016/j.euroneuro.2007.06.005.
J. L. Roffman, A. P. Weiss, S. Purcell, et al., “Contribution of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to negative symptoms in schizophrenia,” Biol. Psychiatry, 63, No. 1, 42–48 (2008), https://doi.org/https://doi.org/10.1016/j.biopsych.2006.12.017.
U. Yadav, P. Kumar, S. Gupta, and V. Rai, “Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis,” Asian J. Psychiatr., 20, 41–51 (2016), https://doi.org/https://doi.org/10.1016/j.ajp.2016.02.002.
I. Dieset, O. A. Andreassen, and U. K. Haukvik, “Somatic comorbidity in schizophrenia: some possible biological mechanisms across the life span,” Schizophr. Bull., 42, No. 6, 1316–1319 (2016), https://doi.org/https://doi.org/10.1093/schbul/sbw028.
H. Kunugi, S. Nanko, and R. M. Myrray, “Obstetric complications and schizophrenia: prenatal underdevelopment and subsequent neurodevelopmental impairment,” Br. J. Psychiatry, 178, Suppl. 40, 5–29 (2001), https://doi.org/https://doi.org/10.1192/bjp.178.40.s25.
L. Yan, L. Zhao, Y. Long, et al., “Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies,” PLoS One, 7, No. 10, e41689 (2012), https://doi.org/https://doi.org/10.1371/journal.pone.0041689.
C. Molloy, R. M. Conroy, D. R. Cotter, and M. Cannon, “Is traumatic brain injury a risk factor for schizophrenia? A meta-analysis of case-controlled population-based studies,” Schizophr. Bull., 37, No. 6, 1104–1110, Epub 2011 Aug 2 (2011), https://doi.org/https://doi.org/10.1093/schbul/sbr091.
A. I. Scher, H. Wu, J. W. Tsao, et al., “MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort,” J. Neurotrauma, 28, No. 9, 1739–1745 (2011), https://doi.org/https://doi.org/10.1089/neu.2011.1982.
V. Glasser, B. Glaser, A. E. Ades, et al., “Perinatal folate-related exposures and risk of psychotic symptoms in the ALSPAC birth cohort,” Schizophr. Res., 120, No. 1–3, 177–183 (2010), https://doi.org/https://doi.org/10.1016/j.schres.2010.03.006.
D. Tiwaria, P. D. Bose, S. Das, et al., “MTHFR (C677T) polymorphism and PR(PROGINS) mutation as genetic factors for preterm delivery, fetal death and low birth weight: A Northeast Indian population based study,” Meta Gene, 3, 31–42 (2015), https://doi.org/https://doi.org/10.1016/j.mgene.2014.12.002.
H. Wu, P. Zhu, X. Geng, et al., “Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis,” Arch. Gynecol. Obstet., 295, No. 5, 1105–1118 (2017), https://doi.org/https://doi.org/10.1007/s00404-017-4322-z.
Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 120, No. 3, Iss. 1, pp. 48–52, March, 2020.
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Korovaitseva, G.I., Gabaeva, M.V. & Golimbet, V.E. Studies of the Association of Genetic Polymorphism C677T in the Methylenetetrahydrofolate Reductase Gene with Symptom Severity in Schizophrenia Patients. Neurosci Behav Physi 51, 7–11 (2021). https://doi.org/10.1007/s11055-020-01031-9
- MTHFR gene
- C677T polymorphism
- genotype-environmental interactions