Document Detail

Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study.
MedLine Citation:
PMID:  15806605     Owner:  NLM     Status:  MEDLINE    
Evidence for an involvement of aberrant homocysteine metabolism in the aetiology of schizophrenia is limited and controversial. A case-control study was performed to quantify the risk of schizophrenia in the presence of elevated homocysteine concentrations or homozygosity for the 677C --> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in subjects of Dutch ancestry. We determined the 677C --> T MTHFR genotype distribution in 254 well-defined patients and 414 healthy controls. Plasma homocysteine concentrations were measured in 62 patients with schizophrenia and 432 control subjects. When homocysteine concentrations were stratified into quartiles of the control distribution, we calculated an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; 95% confidence interval (CI): 1.2-9.2, and OR = 3.1; 95% CI: 1.2-8.0, respectively]. A significant dose-response relation of increasing homocysteine levels and increasing risk for schizophrenia was observed (P = 0.036). The 677TT genotype was associated with an OR of 1.6 [95% CI: 0.96-2.8] of having schizophrenia. Heterozygosity for the T allele compared to 677CC subjects accounted for an OR of 1.3 [95% CI: 0.91-1.8]. Elevated homocysteine levels and the MTHFR 677TT genotype are associated with an increased risk for schizophrenia. These observations support a causal relation between disturbed homocysteine metabolism and schizophrenia.
Jan-Willem Muntjewerff; Mechteld L C Hoogendoorn; René S Kahn; Richard J Sinke; Martin Den Heijer; Leo A J Kluijtmans; Henk J Blom
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  135B     ISSN:  1552-4841     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-25     Completed Date:  2005-05-31     Revised Date:  2008-05-21    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  69-72     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
GGz Nijmegen, Mental Health Institute, Nijmegen, The Netherlands. <>
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MeSH Terms
Case-Control Studies
Gene Frequency
Homocysteine / blood
Hyperhomocysteinemia / complications*
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Middle Aged
Polymorphism, Genetic*
Risk Factors
Schizophrenia / etiology,  genetics*
Reg. No./Substance:
454-28-4/Homocysteine; EC Reductase (NADPH2)

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