Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders

Psychiatr Genet. 2004 Dec;14(4):227-31. doi: 10.1097/00041444-200412000-00012.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cytosine
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • Demography
  • Depressive Disorder / enzymology
  • Depressive Disorder / genetics
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Mood Disorders / enzymology
  • Mood Disorders / genetics*
  • Polymorphism, Single Nucleotide*
  • Reference Values
  • Schizophrenia / enzymology
  • Schizophrenia / genetics*
  • Thymine

Substances

  • Cytosine
  • DNA
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymine