The investigation of the catechol-O-methyltransferase (COMT-[rs4680]) and methylenetetrahydrofolate reductase (MTHFR-[rs1801133]) polymorphisms' interaction might shed light into the pathogenetic mechanisms of the cognitive dysfunction in schizophrenia.
To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients.
However, since our meta-analysis results demonstrated strong support for association of rs1801133 with schizophrenia, further replication studies based on a gene-wide approach need to be considered.
Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele.
A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C --> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects.
The C677T and A1298C mutations of 5,10-methylenetetrahydrofolate reductase (MTHFR) have been linked with conditions such as depression, bipolar disorder, and schizophrenia, but there are not clear the relationship between MTHFR polymorphisms and obsessive-compulsive disorder (OCD).
While C677T is known to play major roles in the risk of adult schizophrenia, our finding for the first time suggests an age-specific association between MTHFR polymorphisms and schizophrenia.
Association study of methylenetetrahydrofolate reductase genetic polymorphism 677C>T with schizophrenia in hospitalized patients in population of European Russia.
MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.
Previous studies suggest that elevated total homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which correlates with plasma total homocysteine levels, are risk factors for schizophrenia (SCZ).
Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95% CI: 1.00-1.59).
Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups.
The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.
The aim was to detect a serum level of Hcy, examine the associations between the level of Hcy, methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and clinical properties for patients with schizophrenia, mood disorders and in a control group.
The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia.
The case-control association study results showed that the MTHFR C677T was associated with schizophrenia (χ(2)=14.11, P=1.74 × 10(-4), OR=0.79; 95% CI=0.70-0.89).
While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world.
A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined.