TY - JOUR
T1 - Maternal MTHFR 677C>T is a risk factor for congenital heart defects
T2 - Effect modification by periconceptional folate supplementation
AU - Van Beynum, Ingrid M.
AU - Kapusta, Livia
AU - Den Heijer, Martin
AU - Vermeulen, Sita H.H.M.
AU - Kouwenberg, Margreet
AU - Daniëls, Otto
AU - Blom, Henk J.
N1 - Funding Information: Conflict of interest: M.d.H. is recipient of a VENI-grant from the Netherlands Foundation of Scientific Research. H.J.B. was Established Investigator of the Netherlands Heart Foundation, as such the principal investigator of the study. None of the authors have any financial or personal interest in the Netherlands Heart Foundation or any other conflict of interest.
PY - 2006/4
Y1 - 2006/4
N2 - Aims: Periconceptional folate supplementation prevents neural tube defects and possibly congenital heart defects (CHD) as well. The search for candidate genes involved in the folate metabolism includes the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism. We studied the association between MTHFR 677C>T variants and CHD risk. The interaction with periconceptional folate supplementation was also investigated. Methods and results: A case-control study and a family-based transmission disequilibrium test (TDT) were conducted to explore this association. In 133 triads, the TDT revealed no association of the fetal 677T allele with the development of a heart defect. In 158 mothers with a CHD-affected child, the maternal MTHFR 677CT and TT genotypes in combination with no use of periconceptional folate supplements were associated with, respectively, a three-fold (OR 3.3 95% CI 1.46-7.32) and six-fold (OR 6.3 95% CI 2.32-17.27) increased risk for conotruncal heart defects in offspring. In a case-only study, the interaction between periconceptional folate supplementation and maternal MTHFR genotype was significant (P = 0.012). Conclusion: The maternal MTHFR 677C>T variants are a risk factor for CHD in offspring, confined to conotruncal heart defects. A gene-environment interaction between maternal MTFHR 677CT and TT genotypes with periconceptional folate supplementation was observed. These findings provide a mechanism of the protective role of folate and support the thesis that periconceptional folate supplementation might prevent CHD.
AB - Aims: Periconceptional folate supplementation prevents neural tube defects and possibly congenital heart defects (CHD) as well. The search for candidate genes involved in the folate metabolism includes the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism. We studied the association between MTHFR 677C>T variants and CHD risk. The interaction with periconceptional folate supplementation was also investigated. Methods and results: A case-control study and a family-based transmission disequilibrium test (TDT) were conducted to explore this association. In 133 triads, the TDT revealed no association of the fetal 677T allele with the development of a heart defect. In 158 mothers with a CHD-affected child, the maternal MTHFR 677CT and TT genotypes in combination with no use of periconceptional folate supplements were associated with, respectively, a three-fold (OR 3.3 95% CI 1.46-7.32) and six-fold (OR 6.3 95% CI 2.32-17.27) increased risk for conotruncal heart defects in offspring. In a case-only study, the interaction between periconceptional folate supplementation and maternal MTHFR genotype was significant (P = 0.012). Conclusion: The maternal MTHFR 677C>T variants are a risk factor for CHD in offspring, confined to conotruncal heart defects. A gene-environment interaction between maternal MTFHR 677CT and TT genotypes with periconceptional folate supplementation was observed. These findings provide a mechanism of the protective role of folate and support the thesis that periconceptional folate supplementation might prevent CHD.
KW - Congenital heart defects
KW - Folate
KW - MTHFR
KW - Periconceptional folate supplementation
UR - http://www.scopus.com/inward/record.url?scp=33645473405&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/eurheartj/ehi815
DO - https://doi.org/10.1093/eurheartj/ehi815
M3 - Article
C2 - 16524890
SN - 0195-668X
VL - 27
SP - 981
EP - 987
JO - European Heart journal
JF - European Heart journal
IS - 8
ER -