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

BackgroundEvidence is emerging for the association of aberrant homocysteine-methylation cycle and increased risk of schizophrenia.MethodsWe 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.ResultsThe 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).ConclusionsOur 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.