Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia.
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.
Muntjewerff
Jan-Willem
JW
GGz Nijmegen, Mental Health Institute, PO Box 7049, 6503 GM Nijmegen, The Netherlands. jmuntjewerff@ggznijmegen.nl
Gellekink
Henkjan
H
den Heijer
Martin
M
Hoogendoorn
Mechteld L C
ML
Kahn
René S
RS
Sinke
Richard J
RJ
Blom
Henk J
HJ
D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002394:Catechol O-Methyltransferase