Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia

Eur Neuropsychopharmacol. 2008 Feb;18(2):99-106. doi: 10.1016/j.euroneuro.2007.06.005. Epub 2007 Aug 22.


Background: Evidence is emerging for the association of aberrant homocysteine-methylation cycle and increased risk of schizophrenia.

Methods: We examined the prevalence of the catechol-O-methyltransferase (COMT) 324G>A (Val108/158Met) and methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms in 252 patients with schizophrenia and 405 control subjects. All subjects were of Dutch ancestry.

Results: The COMT 324AA genotype was not associated with an increased risk of schizophrenia (odds ratio (OR)=1.38 [95% CI: 0.88-2.16], P=0.162), and the MTHFR 677TT genotype showed a nearly significant increased risk for schizophrenia (OR=1.65 [95% CI: 0.97-2.82], P=0.067). The odds ratio for schizophrenia associated with joint occurrence of the COMT 324AA and MTHFR 677TT genotype was 3.08 (95% CI: 1.08-8.76) (P=0.035). Increasing number of low enzyme activity alleles in the COMT and MTHFR genotype combinations were associated with an increased risk of schizophrenia (test for trend, P=0.017).

Conclusions: Our findings do not support a major role for the COMT 324AA and MTHFR 677TT genotype alone, but the combination of both genotypes might increase schizophrenia susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Risk Factors
  • Schizophrenia / epidemiology
  • Schizophrenia / genetics*


  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Catechol O-Methyltransferase