The association between atopy and factors influencing folate metabolism: is low folate status causally related to the development of atopy?

BACKGROUND Deficiency of folate has been associated with several disorders characterized by enhanced activation of the cellular immune system (non-allergic th1 type immune response). Whether folate status is also associated with atopic disease (allergic th2 type immune response) is unknown. We aimed at examining the association between atopy and markers of impaired folate metabolism, i.e. MTHFR(C677T) genotype, plasma total homocysteine, and dietary intakes of methionine, folates, and vitamins B12, B6, and B2. METHODS Cross-sectional population-based study of 1,671 male and female residents of Copenhagen County, Denmark, aged 30-60 years participating in a health examination during 1999-2001. Atopy was defined as positive levels of specific IgE against a panel of inhalant allergens. MTHFR(C677T) genotype was determined by PCR followed by restriction fragment length polymorphism analyses. Total homocysteine was measured by fluorescent polarization immunoassay. Dietary vitamin intakes were estimated from a semi-quantitative food frequency questionnaire. RESULTS The prevalence of atopy was associated with MTHFR(C677T) genotype. TT individuals had a significantly higher risk of atopy compared with CC/CT individuals [odds ratio 1.76, 95% confidence interval (95% CI) 1.19-2.60]. Additionally, gene-diet interaction effects were identified. Dietary markers were negatively associated with risk of atopy in persons with the TT genotype. Total homocysteine was not related to atopy (odds ratio per 5 mumol/l = 1.12, 95% CI 0.98-1.29). CONCLUSIONS The results suggest that an impaired folate metabolism may be causally related to the development of atopy.