Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia

Muntjewerff, Jan-Willem; Put, Nathalie van der; Eskes, T.K.A.B.; Ellenbroek, Bart A.; Steegers, Eric A.P.; Blom, Henk J.; Zitman, Frans G.

doi:10.1016/s0165-1781(03)00200-2

Cited by 62 publications

(45 citation statements)

References 31 publications

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“…Data for the meta-analysis were obtained from eight published case-control studies 22,[29][30][31][32][33][34][35] with a total number of 812 cases and 2113 control subjects. Figure 1 shows the ORs and 95% CIs of schizophrenia associated with a 5 mmol/l increase in measured plasma total homocysteine, separately for individual studies and for all studies when taken together.…”

Section: Homocysteine and Schizophreniamentioning

confidence: 99%

“…A total of nine published articles 22,31,33,[36][37][38][39][40][41] reported on the relationship between schizophrenia and the MTHFR 677C4T polymorphism. One article provided data on two separate studies.…”

Section: Mthfr and Schizophreniamentioning

confidence: 99%

“…Susser et al 30 Regland et al 29 Muntjewerff et al 33 Muntjewerff et al 22 Goff et al 35 Virgos et al 31 Applebaum et al 34 Levine Figure 1 Odds ratios (ORs) and 95% confidence intervals (CIs) of schizophrenia for a 5 mmol/l increase in plasma total homocysteine concentration for each study separately and combined (Studies are ordered by the inverse of the s.e. of each estimate.…”

Section: Studymentioning

confidence: 99%

“…Muntjewerff et al 33 Muntjewerff et al 22 Yu et al, Chinese series 40 Yu et al, Scottish series 40 Tan et al 41 Joober et al 38 Sazci et al 39 Virgos et al 31 Kunugi et al 37 Arinami Figure 2 Odds ratios (ORs) and 95% confidence intervals (Cls) of schizophrenia for TT versus CC genotype of the MTHFR 677C4T polymorphism of each study seperately and combined (Studies are ordered by the inverse of the s.e. of each estimate.…”

Section: Combinedmentioning

confidence: 99%

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Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Muntjewerff¹,

et al. 2005

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Elevated plasma homocysteine concentration has been suggested as a risk factor for schizophrenia, but the results of epidemiological studies have been inconsistent. The most extensively studied genetic variant in the homocysteine metabolism is the 677C4T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, resulting in reduced enzyme activity and, subsequently, in elevated homocysteine. A meta-analysis of eight retrospective studies (812 cases and 2113 control subjects) was carried out to examine the association between homocysteine and schizophrenia. In addition, a meta-analysis of 10 studies (2265 cases and 2721 control subjects) on the homozygous (TT) genotype of the MTHFR 677C4T polymorphism was carried out to assess if this association is causal. A 5 lmol/l higher homocysteine level was associated with a 70% (95% confidence interval, CI: 27-129) higher risk of schizophrenia. The TT genotype was associated with a 36% (95% CI: 7-72) higher risk of schizophrenia compared to the CC genotype. The performed meta-analyses showed no evidence of publication bias or excessive influence attributable to any given study. In conclusion, our study provides evidence for an association of homocysteine with schizophrenia. The elevated risk of schizophrenia associated with the homozygous genotype of the MTHFR 677C4T polymorphism provides support for causality between a disturbed homocysteine metabolism and risk of schizophrenia.

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Section: Homocysteine and Schizophreniamentioning

confidence: 99%

Section: Mthfr and Schizophreniamentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Combinedmentioning

confidence: 99%

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Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Muntjewerff¹,

et al. 2005

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“…In addition, the evaluation of an entire metabolic pathway, as opposed to isolated single gene products, provides greater mechanistic insights into disease pathology and can identify new options for targeted intervention strategies. We have used a targeted approach to "metabolomics" by focusing on the dynamics of a single metabolic pathway involving methionine transmethylation and transsulfuration that has been implicated in the pathogenesis of numerous other neurologic disorders (Miller 2003;Serra et al 2001;Schulz et al 2000;Muntjewerff et al 2003;Pogribna et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism

James

Melnyk

Jernigan

et al. 2006

American J of Med Genetics Pt B

531

550

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Autism is a behaviorally-defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G>A), transcobalamin II (TCN2 776G>C), catechol-O-methyltransferase (COMT 472G>A), methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C), and GST M1. We propose that an increased vulnerability to

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A meta‐analysis of the MTHFR C677T polymorphism and schizophrenia risk

Lewis

Zammit

Gunnell

et al. 2005

American J of Med Genetics Pt B

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Epigenetic mechanisms such as methylation of DNA, could lead to abnormal neurodevelopment and may be important in the etiology of schizophrenia. Maternal dietary folate intake may play a role in determining methylation levels. The MTHFR gene C677T polymorphism influences folate metabolism and intracellular availability of folate metabolites for methylation. We carried out a meta-analysis of MTHFR C677T genotype and schizophrenia risk, and found that TT homozygotes had a significantly increased risk, OR 1.48 (1.18-1.86). This supports the hypothesis that folate status is a determinant of schizophrenia risk. Larger studies of this issue are required, together with studies of maternal genotype which could identify whether maternal folate status during pregnancy is important.

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Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia

Cited by 62 publications

References 31 publications

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism

A meta‐analysis of the MTHFR C677T polymorphism and schizophrenia risk

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