Congenital heart defects and biomarkers of methylation in children: a case-control study

Eur J Clin Invest 2011; 41 (2): 143–150 Background Derangements in the maternal methylation pathway, expressed by global hypomethylation and hyperhomocysteinemia, are associated with the risk of having a child with a congenital heart defect (CHD). It is not known whether periconception exposure to these metabolic derangements contributes to chromosome segregation and metabolic programming of this pathway in the foetus. Design In a Dutch population‐based case–control study of 143 children with CHD and 186 healthy children, we investigated S‐adenosylmethionine (SAM), S‐adenosylhomocysteine (SAH), total homocysteine (tHcy), the vitamins folate and B12 and the functional single nucleotide polymorphisms in the folate gene MTHFR 677C>T and 1298A>C. Comparisons were made between cases and controls adjusting for age, medication, vitamin use and CHD family history. Results In the overall CHD group, the median concentrations of SAM (P = 0·011), folate in serum (P = 0·021) and RBC (P = 0·030) were significantly higher than in the controls. Subgroup analysis showed that this was mainly attributable to complex CHD with higher SAM (P