Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders.
OBJECTIVE
An elevated homocysteine level has been reported for patients with schizophrenia and depression. We investigated the frequency of the common C667 T variant of the enzyme methylenetetrahydrofolate reductase in controls and patients of Chinese descent.


METHODS
Controls with no history of mental disorder and patients diagnosed with schizophrenia, bipolar and unipolar disorders were recruited. Genomic DNA from all were genotyped for the C667 T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
There was no significant difference in genotype distributions or allele frequencies between controls and any of the diagnostic groups, although the frequency of the T allele was higher for all diagnostic groups and for both the male and female genders. When data was analyzed with the minor T allele as dominant, there was an excess of the T-containing genotypes in each of the patient groups compared with controls. For the difference between controls and all cases combined it almost reached statistical significance (P=0.077), with an odds ratio of 1.46 (95% confidence interval, 0.96-2.22).


CONCLUSIONS
Although there was no significant association as measured by the P value, the odds ratio and confidence interval provided some evidence of increased risk for individuals with the T-containing genotypes. A minor role for this polymorphism in the pathogenesis of schizophrenia and depression could not be ruled out and would warrant further investigation.
Tan
Ene-Choo
EC
Defence Medical Research Institute, Defence Science and Technology Agency, Republic of Singapore. tenechoo@dso.org.sg
Chong
Siow-Ann
SA
Lim
Lionel C C
LC
Chan
Angelina O M
AO
Teo
Yik-Ying
YY
Tan
Chay-Hoon
CH
Mahendran
Rathi
R
D000328:Adult; D000483:Alleles; D003596:Cytosine; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003710:Demography; D003866:Depressive Disorder / Q000201:enzymology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D019964:Mood Disorders / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D013941:Thymine
D003596:Cytosine; D004247:DNA; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine