Does the Interaction between Maternal Folate Intake and the Methylenetetrahydrofolate Reductase Polymorphisms Affect the Risk of Cleft Lip with or without Cleft Palate?

• Published in: American journal of epidemiology Vol. 157; no. 7; pp. 583 - 591
• Main Authors: van Rooij, Iris A. L. M., Vermeij-Keers, Christl, Kluijtmans, Leo A. J., Ocké, Marga C., Zielhuis, Gerhard A., Goorhuis-Brouwer, Sieneke M., van der Biezen, Jan-Jaap, Kuijpers-Jagtman, Anne-Marie, Steegers-Theunissen, Régine P. M.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.04.2003; Oxford Publishing Limited (England)
• Subjects: abnormalities; Biological and medical sciences; Case-Control Studies; CL(P); Cleft Lip - complications; Cleft Lip - genetics; Cleft Lip - prevention & control; cleft lip with or without cleft palate; Cleft Palate - complications; Cleft Palate - genetics; Cleft Palate - prevention & control; confidence interval; Confidence Intervals; Diseases of mother, fetus and pregnancy; Female; folic acid; Folic Acid - administration & dosage; Folic Acid - genetics; Folic Acid - therapeutic use; genes; Genotype; Gynecology. Andrology. Obstetrics; Humans; Infant, Newborn; Male; Maternal Nutritional Physiological Phenomena; Medical sciences; methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2); MTHFR; nutrition; odds ratio; Oxidoreductases Acting on CH-NH Group Donors - deficiency; Oxidoreductases Acting on CH-NH Group Donors - genetics; Polymorphism, Genetic; Pregnancy; Pregnancy. Fetus. Placenta; vitamins; Human; Methylenetetrahydrofolate reductase (NADPH); Cleft lip; Pregnancy disorders; Enzyme; genes; abnormalities; pregnancy; Epidemiology; Congenital disease; Folic acid; nutrition; Newborn; Gene; Diet; vitamins; Food intake; Malformation; Risk factor; Oxidoreductases; Public health; Polymorphism
• ISSN: 0002-9262; 1476-6256; 0002-9262
• DOI: 10.1093/aje/kwg005

Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998–2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.