A variant of the 5,10-Methylenetetrahydrofolate reductase (MTHFR) gene, which results in the production of a mildly dysfunctional thermolabile enzyme, is not associated with clinically significant bipolar disorder, study findings confirm.

The MTHFR 677TT genotype has been associated with a significant elevation in the circulating concentrations of homocysteine and linked with lower levels of red blood cell folate, plasma folate, and vitamin B12, the researchers explain.

“This may parallel a similar reduction in 5-methyltetrahydrofolate in the central nervous system and lead to a reduction in methyl group donors and monoamine neurotransmitter function, which in turn may elevate the risk of bipolar disorder,” they say.

Sarah Cohen-Woods, from King’s College London, UK, and colleagues carried out an association study of the MTHFR C677T polymorphism in 897 patients with bipolar I or bipolar II disorder and 1687 mentally healthy control individuals.

They found no significant difference in the genotype and allele frequencies of the C677T polymorphism between the patients with bipolar disorder and the controls, with 45.6% of patients in each group carriers of the CT genotype.

The researchers also carried out a meta-analysis of eight previously published articles that investigated the C677T polymorphism in bipolar disorder, involving 2303 patients with the disorder and 3725 mentally healthy individuals.

No increased risk for bipolar disorder was found in carriers of the 677T allele, the 677TT genotype, or when the 677TT and 677CT genotypes were combined.

The researchers suggest in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics that any previous associations between bipolar disorder and the MTHFR 677TT genotype could simply be “a consequence of chance, or a consequence of the polymorphism being associated with another disease that is highly associated with bipolar disorder, as with depression.”

They conclude: “The observed data, and our reanalysis of those of others, make it unlikely that the MTHFR C677T polymorphism influences the risk of bipolar disorder.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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