To evaluate the effects on anencephaly risk of the interaction between the maternal profile of folate, vitamin B12 and homocysteine and the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR).

Case–control study paired (1:1) on maternity clinic, date of birth and state of residence. Cases of anencephaly were identified using the Registry of the Mexican Neural Tube Defect Epidemiological Surveillance System. Case and control mothers were selected from the same maternity departments. All mothers completed a structured questionnaire and blood samples were obtained to determine the MTHFR 677C→T polymorphism and biochemical profile.

Mexico, Puebla and Guerrero states, Mexico.

A total of 151 mothers of cases and controls were enrolled from March 2000 to February 2001. We had complete information on biochemical profile and MTHFR C677T polymorphism for ninety-eight mothers of cases and ninety-one mothers of controls.

The adjusted models show that the risk of anencephaly in mothers with 677TT genotype was reduced by 18 % (OR = 0·82; 95 % CI 0·72, 0·94) for each 1 ng/ml increment in serum folate. In terms of tertiles, mothers with 677TT genotype with serum folate levels in the upper tertile (>14·1 ng/ml) had a 95 % lower risk to have a child with anencephaly than mothers with serum folate levels in the first and second tertiles (P trend = 0·012).

Our data agree with the hypothesis of a gene–nutrient interaction between MTHFR 677C→T polymorphism and folate status. We observed a protective effect on anencephaly risk only in mothers with 677TT genotype as serum folate levels increased.