Maternal MTHFR 677C>T is a risk factor for congenital heart defects: Effect modification by periconceptional folate supplementation

European Heart Journal

Volumn 27, Issue 8, 2006, Pages 981-987

  Van Beynum, Ingrid M ^a   Kapusta, Livia ^a   Den Heijer, Martin ^a   Vermeulen, Sita H H M ^a   Kouwenberg, Margreet ^a   Daniëls, Otto ^a   Blom, Henk J ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Congenital heart defects; Folate; MTHFR; Periconceptional folate supplementation

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); FOLIC ACID; GENOMIC DNA; VITAMIN B GROUP;

ADULT; ARTICLE; BODY MASS; CASE CONTROL STUDY; CHILD; CONGENITAL HEART DISEASE; CONTROLLED STUDY; DIET SUPPLEMENTATION; DISEASE ASSOCIATION; FALLOT TETRALOGY; GENETIC POLYMORPHISM; GENOTYPE; GREAT VESSELS TRANSPOSITION; HEART ATRIUM SEPTUM DEFECT; HEART VENTRICLE SEPTUM DEFECT; HUMAN; LUNG ATRESIA; MAJOR CLINICAL STUDY; PATENT DUCTUS ARTERIOSUS; PRIORITY JOURNAL; RISK FACTOR; VITAMIN INTAKE;

ADOLESCENT; ADULT; AGED; CASE-CONTROL STUDIES; CHILD; CHILD, PRESCHOOL; DIETARY SUPPLEMENTS; FEMALE; FOLIC ACID; FOLIC ACID DEFICIENCY; HEART DEFECTS, CONGENITAL; HUMANS; INFANT; INFANT, NEWBORN; MALE; MATERNAL NUTRITION PHYSIOLOGY; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; POLYMORPHISM, GENETIC; PRECONCEPTION CARE; RISK FACTORS;

EID: 33645473405     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehi815     Document Type: Article

References (38)

1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890-1900.
2. Tennstedt C, Chaoui R, Körner H, Dietel M. Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study. Heart 1999;82:34-39.
3. Czeizel AE. Periconceptional folic acid containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol 1998;78:151-161.
4. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol 2000;151:878-884.
5. Czeizel AE, Dobo M, Vargha P. Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities. Birth Defects Res (Part A) 2004;70:853-861.
6. Rosenblatt DS. Inherited disorders of folate transport and metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. Disorders of Transsulfaration. New York: McGraw-Hill; 1995. p3111-3128.
7. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-113.
8. Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol 1999;6:359-365.
9. Molloy AM, Daly S, Mills JL, Kirke PN, Whitehead AS, Ramsbottom D, Conley MR, Weir DG, Scott JM. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates; implications for folate intake recommendations. Lancet 1997;349:1591-1593.
10. van der Put NMJ, Steegers-Theunissen RPM, Frosst P, Trijbels FJM, Eskes TKAB, vanden Heuvel LP, Mariman ECM, den Heijer M, Rozen R, Blom HJ. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995;346:1070-1071.
11. Junker R, Kotthoff S, Vielhaber H, Halimeh S, Kosch A, Koch HG, Kassenbohmer R, Heineking B, Nowak-Gottle U. Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease. Cardiovasc Res 2001;51:251-254.
12. Wenstrom KD, Johanning GL, Johnston KE, DuBard M. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol 2001;184:806-817.
13. Storti S, Vittorini S, Iascone MR, Sacchelli M, Collavoli A, Ripoli A, Cocchi G, Biagini A, Clerico A. Association between 5,10- methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and conotruncal heart defects. Clin Chem Lab Med 2003;41:276-280.
14. Kapusta L, Haagmans ML, Steegers EA, Cuypers MH, Blom HJ, Eskes TK. Congenital heart defects and maternal derangement of homocysteine metabolism. J Pediatr 1999;135:773-774.
15. Hobbs C, Cleves MA, Melnyk S, Zhao W, James JS. Congenital heart defects and abnormal maternal biomarkers of methionine and homocysteine metabolism. Am J Clin Nutr 2005;81:147-153.
16. Spiegelstein O, Mitchell LE, Merriweather MY, Wicker NJ, Zhang Q, Lammer EJ, Finnell RH. Embryonic development of folate binding protein-1 (Folbp1) knockout mice: Effects of the chemical form, dose, and timing of maternal folate supplementation. Dev Dyn 2004;231:221-231.
17. Tang LS, Wlodarczyk BJ, Santillano DR, Miranda RC, Finnell RH. Development consequences of abnormal folate transport during murine heart morphogenesis. Birth Defects Res (Part A) 2004;70:449-458.
18. Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proc Natl Acad Sci USA 1996;93:15227-15232.
19. Boot MJ, Steegers-Theunissen RPM, Poelmann RE, van Iperen L, Lindemans J, Gittenberger-de Groot AC. Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro. Dev Dyn 2003;227:301-308.
20. Tierney BJ, Ho T, Reedy MV, Brauer PR. Homocysteine inhibits cardiac neural crest cell formation and morphogenesis in vivo. Dev Dyn 2004;229:63-73.
21. Kirby ML, Turnage KL, Hays B. Characterization of conotruncal malformations following ablation of cardiac neural crest. Anat Rec 1985;213:87-93.
22. Besson WT, Kirby ML, van Mierop LHS, Teabeaut JR II. Effects of the size of lesions of the cardiac neural crest at various embryonic ages on incidence and type of cardiac defects. Circulation 1986;73:360-364.
23. Yelbuz TM, Waldo KL, Kumiski DH, Stadt HA, Wolfe RR, Leatherbury L, Kirby ML. Shortened outflow tract leads to altered cardiac looping after neural crest ablation. Circulation 2002;106:504-510.
24. van Beynum IM, den Heijer M, Thomas CMG, Afman L, Oppenraay-van Emmerzaal D, Blom HJ. Total homocysteine and its predictors in Dutch children. Am J Clin Nutr 2005;81:1110-1116.
25. Keijzer MB, den Heijer M, Blom HJ, Bos GM, Willems HP, Gerrits WB, Rosendaal FR. Interaction between hyperhomocysteinemia, mutated methylenetetrahydrofolatereductase (MTHFR) and inherited thrombophilic factors in recurrent venous thrombosis. Thromb Haemost 2002;88:723-728.
26. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
27. Schlesselman JJ. Sample size requirements in cohort and case-control studies of disease. Am J Epidemiol 1974;99:381-384.
28. Gattto NM, Campbell UB, Rundle A, Ahsan H. Further development of the case-only design for assessing gene-environment interaction: evaluation of and adjustment for bias. Int J Epidemiol 2004;33:1014-1024.
29. Spielman RS, McGinnis RE, Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;52:506-516.
30. Ewens WJ, Spielman RS. The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet 1995;57:455-464.
31. van der Put NMJ, Eskes TKAB, Blom HJ. Is the common C677T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis. QJM 1997;90:111-115.
32. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C>T polymorphism and risk of coronary heart disease. A meta-analysis. JAMA 2002;288:2023-2031.
33. Gezondheidsraad/Voedingsraad. Vervolgadvies inzake foliumzuurvoorziening in relatie tot neurale buisdefecten. (Advice concerning folic acid intake in respect of neural tube defects.) The Hague: Voorlichtingsbureau voor de Voeding, 1993 (in Dutch).
34. Sacchi E, Tagliabue L, Duca F, Mannucci PM. High frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Northern Italy. Thromb Haemost 1997;78:963-964.
35. Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM, Weir DG, Shields DC, Scott JM. A genetic defect in 5,10-methylenetetrahydrofolate reductase in neural tube defects. QJM 1995;88:763-766.
36. van Mierop L, Kutsche LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol 1986;58:133-137.
37. Waldo K, Miyagawa-Tomita S, Kumiski D, Kirby ML. Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure. Dev Biol 1998;196:129-144.
38. Poelmann RE, Gittenberger-de Groot AC. A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: multiple functions in heart development? Dev Biol 1999;207:271-286.