Gene Report

Basic Info
Approved Symbol MTHFR
Approved Name methylenetetrahydrofolate reductase (NAD(P)H)
Previous Name 5,10-methylenetetrahydrofolate reductase (NADPH)
Location 1p36.3
Position chr1:11785723-11806920, -1
External Links HGNC: 7436
Entrez Gene: 4524
Ensembl: ENSG00000177000
UCSC: uc001atc.2
No. of Studies 16 (Positive: 10; Negative: 6; trend: 0)
Overlap with SZ? YES
Overlap with MDD? YES
Gene related studies (count: 16)
Reference Tested Markers Statistical Values/Author Comments Result Category Comment on Study
Tan, E. C., 2004 Other variant: MTHFR_C677T There was no significant difference in genotype distributions or allele frequencies of the MTHFR 667C>T polymorphism between controls and any of the diagnostic groups. Negative Comment on Study
Kunugi, H., 1998 Other variant: MTHFR_C677T Our results suggest that homozygosity for the T677 allele of the MTHFR gene is unlikely to play a major role in the pathogenesis of schizophrenia or affective disorders in our sample. Negative Comment on Study
Gilbody, S., 2007 Other variant: MTHFR_C677T For bipolar disorder and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.82 (95% CI: 1.22, 2.70), with low heterogeneity (I<sup>2</sup>= 42%)—based on 550 cases and 1, 098 controls. . These results were robust to various sensitively analyses. This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention. Positive Comment on Study
El-Hadidy, M. A., 2013 Other variant: MTHFR_C677T The present findings suggest that the MTHFR C677T polymorphism is likely associated with the risk of developing BD and schizophrenia, and influences the age at onset of schizophrenia but not the age at onset of BD. Positive Comment on Study
Arinami, T.,1997 Other variant: MTHFR_C677T No significant differences were found in bipolar groups for MTHFR gene. Negative Comment on Study
Kempisty, B., 2007 (a) Other variant: MTHFR_A1298C The results confirm association of BD with the 1p36.3 MTHFR locus and with the methyl group transfer using folatedependent one-carbon pathway. Positive Comment on Study
Kempisty, B., 2006 Other variant: MTHFR_C677T The data may suggest the association of homozygous 677TT genotype of MTHFR gene with bipolar disorder and schizophrenia. Positive Comment on Study
Zintzaras, E., 2006 Other variant: MTHFR_C677T The meta-analysis results suggested that east Asians have a greater genetic risk from the MTHFR gene in developing schizophrenia and depression, and that the genetic effects in bipolar disorder and depression are different. A further exploration of the involvement of the MTHFR gene in the susceptibility to schizophrenia and affective disorders, with a greater number of studies with larger sample sizes, however, are needed to fully establish the role of the MTHFR gene. Positive Comment on Study
Reif, A.,2005 Other variant: MTHFR_C677T, MTHFR_A1298C The 1298C variant was significantly associated with both Bip and MD arguing that variation in the MTHFR gene contributes to the genetic risk for affective psychoses. Positive Comment on Study
Peerbooms, O. L.,2011 Other variant: MTHFR_A1298C There was evidence for diagnostic moderation indicating a significant association with BPD Positive Comment on Study
Rai, V.,2011 Other variant: MTHFR_C677T It shows meager association between MTHFR C677T genotype and bipolar disorder. Positive Comment on Study
Cohen-Woods, S.,2010 Other variant: MTHFR_C677T Our findings suggest that the MTHFR C677T polymorphism is not involved in the genetic etiology of clinically significant BD. Negative Comment on Study
Yosifova, A.,2009 SNP: rs1801133 No SNP of this gene had significant association with BD in our population. Negative Comment on Study
Chen, Z.,2009 Other variant: MTHFR_C677T In conclusion, pooled analysis of data from seven studies indicates MTHFR C677T is not significantly associated with bipolar disorder. Genome wide association studies also did not find any clues between markers of MTHFR gene and bipolar. Although MTHFR C677T is associated with schizophrenia by other metaanalysis, our data suggest no evidence for a major role of this polymorphism in the pathogenesis of bipolar disorder. The results implied different genetic background of schizophrenia and bipolar disorder to some extent. Negative Comment on Study
Wang, L. J., 2015 Other variant: MTHFR_C677T Our findings support preliminary evidence that the COMT and MTHFR genes interact in BP-II, and they imply the connection of both dopaminergic pathways and methylation pathways in the pathogenesis of BP-II. Logistic regression analysis showed a significant interaction effect of the COMT Val158Met Val/Val genotype and the MTHFR C677T C/T + T/T genotype for the protective effect on the odds of developing BP-II. Positive Comment on Study
Hu C.Y., 2014 Other variant: MTHFR_exon 4_C677T, MTHFR_exon 7_A1298C We conclude that MTHFR polymorphism is associated with BPD among Asian, African populations, but not the white. Positive Comment on Study
Gene functional annotation
Gene related GO terms (count: 27)

GO terms by PBA (count: 0)

GO terms by database search (count: 27)

Gene related KEGG pathways (count: 2)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 2)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 0)

Related other genetic factors
Gene related SNPs (count: 1)

Literature-origin SNPs (count: 1)

LD-proxies (count: 0)

Gene related CNVs (count: 0)

Gene related other variants (count: 4)

Gene related regions (count: 5)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)
Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 10)

Overlap with SZ from candidate gene intersection analysis (count: 23)

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 6)

Overlap with MDD from candidate gene intersection analysis (count: 2)

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Region: chr1:11785723..11806920 View in gBrowse
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