Up until now, only approximately 15% of the CHD can be attributed to a known cause. The remaining 85% is thought to result from interactions between genetic predispositions and periconception environmental exposures. Folate, a B vitamin involved in the one-carbon metabolism, has been associated with CHD. Therefore, we hypothesize that derangements in one-carbon metabolism due to genetic polymorphisms and environmental exposures, are associated with CHD. This hypothesis was tested in the HAVEN-study: a case-control triad study comparing risk factors between approximately 250 case children and 300 control children with both parents. We found that maternal hyperhomocysteinemia is a risk factor for CHD. Maternal hypomethylation seems a risk factor for CHD and Down Syndrome, while hypermethylation in children seems to contribute to nonisolated CHD. We have also found that the MTHR C677T, MTRR A66G and TC C776G polymorphisms are not strong risk factors for CHD. I! nterestingly, the MTHFR 1298 C-allele of the father and the child decreased CHD risk by 40% and 30% respectively. Moreover, an almost nine fold increased risk of CHD was found if the child carried the NNMT AG/AA genotype and was exposed to medicines and low intakes of vitamin B3. In conclusion, it seems that genetic variants that play a role in the one-carbon metabolism, together with lifestyle factors, such as the use of medicines and a suboptimal vitamin B status, are involved in the development of CHD.

congenital heart diseases, life style, methylation, nutrients, polymorphisms, risk factors
E.A.P. Steegers (Eric) , W.A. Helbing (Willem)
Erasmus University Rotterdam
The financial support of the Erasmus University Rotterdam, the department of Obstetrics and Gynecology, and Pediatric Cardiology is gratefully acknowledged. Finally, the following sponsors are gratefully acknowledged: ing. A.H.C. van Driel & Mw. L.H.I.M. Zuiderent, Dhr. P.B.A.A. van Driel, Mw. C.F.L.M. van Driel, ir. J.W.H. Korstanje, ir. J.J.A. van der Wal
978-90-8559-567-0
hdl.handle.net/1765/17118
Erasmus MC: University Medical Center Rotterdam

van Driel, L.M.J.W. (2009, November 3). Methylation, Lifestyle and Genes in the Pathogenesis and Prevention of Human Congenital Heart Diseases. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/17118