Association between variants of MTHFR genes and psychiatric disorders: A meta-analysis

Abstract

BackgroundPsychiatric disorders have seriously affected human life, one of the risk genes related to psychosis is the methylenetetrahydrofolatereductase (MTHFR) gene. This gene has a potential role in psychiatric disorders. Therefore, a meta-analysis is conducted to investigate the correlations between two prevalent MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T, A1298C, severe psychological disorders (schizophrenia, major depression, bipolar disorder).MethodsA total of 81 published studies were screened and selected by a search of electronic databases up to April 2022. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR polymorphism and psychiatric disorders susceptibility by using random effect models.ResultsWe found that MTHFR C677T polymorphism is significantly related to schizophrenia and major depression in the overall population. MTHFR C677T has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia and major depression significantly correlate with MTHFR C677T and A1298C in Asian populations but not Caucasians. Besides, schizophrenia is correlated substantially with MTHFR C677T in the African population. However, the MTHFR A1298C polymorphism is only marginally linked to major depression.ConclusionFindings of the current study revealed that MTHFR may contribute to the common pathogenesis of psychiatric diseases and that its variants may be essential in controlling the expression of psychosis-related genes. This study could help the researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.

Molecular Dynamics Study of Human MTHFR Wild-Type and A222V Mutant-Type: A Computational Approach

“…MTHFR A222V has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia for T vs. C: OR = 1.19, 95% CI = 1.11-1.29, P < 0.001; for TT + CT vs. CC: OR = 1.22, 95% CI = 1.10-1.35, P < 0.001; for TT vs. CT + CC: OR = 1.31, 95% CI = 1.16-1.48, P < 0.001; for TT vs. CC: = 1.46, 95% CI = 1.24-1.72, P < 0.001 and major depression for T vs. C: OR = 1.46, 95% CI = 1.21-1.77, P < 0.001; for TT + CT vs. CC: OR = 1.52, 95% CI = 1.11-2.08, P = 0.009; for TT vs. CT + CC: OR = 1.75, 95% CI = 1.34-2.28, P < 0.001; for TT vs. CC: OR = 1.89, 95% CI = 1.40-2.57, P < 0.001 significantly correlate with MTHFR A222V in Asian populations (Zhang et al, 2022).…”

“…The relationship between the MTHFR A222V polymorphism and disease might be associated with two aspects involving homocysteine concentration and altered metabolism of folates and homocysteine (Ueland et al, 2001). The disease that might be involved such as diabetic neuropathy (Wu et al, 2017;Yigit et al, 2013), congenital heart disease (CHD) (Xuan et al, 2014), renal failure (Hishida et al, 2013), cancer (He et al, 2017;Kumar et al, 2018;Li et al, 2021), psychiatric disorders (Zhang et al, 2022), etc. This genetic variation requires further exploration regarding the risk of changes in protein structure and stability.…”

Genetic and Epigenetic Factors Associated with Postpartum Psychosis: A 5-Year Systematic Review

“…Genetics, epigenetics, neuroactive molecules, psychiatric history, social support, heath history, use of substances, and adverse life events belong under this branch. Regarding genetics, DNA is an essential baseline for the possible development of diseases [11]. Recent research has shown that 49% of individuals diagnosed with PPP have a history of BD [11].…”

“…Regarding genetics, DNA is an essential baseline for the possible development of diseases [11]. Recent research has shown that 49% of individuals diagnosed with PPP have a history of BD [11]. In cases of full blood siblings where one sister developed PPP, which was triggered during childbirth, higher chances of PPP development are noted for the other sister compared with the rate of occurrence in non-related individuals [12].…”

Abnormalities in one-carbon metabolism in young patients with psychosis

“…Folates, the main players in C1 metabolism, are essential for monoamine synthesis and genome stability, as they regulate DNA synthesis, repair, and methylation. Dihydrofolate, the form of folate naturally present in our diet ( 3 ), is gradually converted into L-methylfolate in the digestive tract by the methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes of this metabolism ( 4 ), which gene is associated with schizophrenia ( 5 ). L-methylfolate is the main active form of folate available in the body, it crosses the blood-brain barrier and is converted into tetrahydrofolate.…”