Are genes connected with homocysteine metabolism associated with bipolar disorder?

Increased levels of homocysteine have been observed in various psychiatric disorders, among them in schizophrenia, depression and bipolar mood disorder. Of the genes connected with homocysteine metabolism, some studies have found an association between polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and bipolar disorder. The aim of this study was to investigate a possible association between 5 polymorphisms of 4 genes coding enzymes of homocysteine metabolism and bipolar disorder.

A total of 120 patients with bipolar disorder (24 male, 96 female) and 167 subjects from the general population (81 male, 86 female) were included in the study. Genotyping was performed for the C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene, for the T833C polymorphism (rs5742905) of the cystathionine-β-synthase (CBS) gene, for the A2756G polymorphism (rs1805087) of the homocysteine methyltransferase gene, and for the A66G polymorphism (rs1801394) of the methionine synthase reductase (MTRR) gene.

An association with bipolar disorder was found for the T833C polymorphism (rs5742905) of the CBS gene. However, in the patient sample, the genotypes of this polymorphism were not in Hardy-Weinberg equilibrium. No relationship to bipolar disorder was obtained for the remaining polymorphisms studied.

These results are the first suggesting a possible association between T833C polymorphism (rs5742905) of the CBS gene and bipolar disorder. We were unable to confirm an association between bipolar disorder and C677T polymorphism (rs1801133) of the MTHFR gene, as suggested in some previous studies.