Methylenetetrahydrofolate reductase 677C→T polymorphism affects DNA methylation in response to controlled folate intake in young women

• Published in: The Journal of nutritional biochemistry Vol. 15; no. 9; pp. 554 - 560
• Main Authors: Shelnutt, Karla P., Kauwell, Gail P.A., Gregory, Jesse F., Maneval, David R., Quinlivan, Eoin P., Theriaque, Douglas W., Henderson, George N., Bailey, Lynn B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2004; Elsevier Science
• Subjects: Adult; Biological and medical sciences; blood serum; Cytosine - metabolism; DNA methylation; erythrocytes; Erythrocytes - drug effects; Erythrocytes - metabolism; Feeding study; Feeding. Feeding behavior; Female; Folic acid; Folic Acid - blood; Folic Acid - pharmacokinetics; Folic Acid - pharmacology; Folic Acid Deficiency - genetics; Folic Acid Deficiency - metabolism; Fundamental and applied biological sciences. Psychology; genetic polymorphism; Genotype; homocysteine; Homocysteine - blood; Humans; Leukocytes - drug effects; Leukocytes - physiology; methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - drug effects; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; MTHFR; nutrient intake; nutrition-genotype interaction; Polymorphism, Single Nucleotide; Vertebrates: anatomy and physiology, studies on body, several organs or systems; vitamin deficiencies; vitamin metabolism; women; young adults; Young women; DNA methylation; MTHFR; Genotype; Feeding study; Young women; Folic acid; Human; Methylenetetrahydrofolate reductase (NADPH); Feeding behavior; Enzyme; Folate; Feeding; DNA; Female; Oxidoreductases; Methylation; Polymorphism
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2004.04.003

DNA methylation is critical for normal genomic structure and function and is dependent on adequate folate status. A polymorphism (677C→T) in a key folate enzyme, methylenetetrahydrofolate reductase (MTHFR), may impair DNA methylation when folate intake is inadequate and may increase the risk of reproductive abnormalities. The present study was designed to evaluate the effect of the MTHFR 677C→T polymorphism on changes in global DNA methylation in young women consuming a low folate diet followed by repletion with the current Recommended Dietary Allowance (RDA). Women (age 20–30 years) with the TT (variant; n = 19) or CC ( n = 22) genotype for the MTHFR 677C→T polymorphism participated in a folate depletion-repletion study (7 weeks, 115 μg DFE/day; 7 weeks, 400 μg DFE/day). DNA methylation was measured at baseline, week 7, and week 14 using a [ 3H]methyl acceptance assay and a novel liquid chromatography tandem mass spectrometry assay of the DNA bases methylcytosine and cytosine. [ 3H]Methyl group acceptance tended to increase ( P = 0.08) during depletion in all subjects, indicative of a decrease in global DNA methylation. During repletion, the raw change and the percent change in the methylcytosine/total cytosine ratio increased ( P = 0.03 and P = 0.04, respectively) only in the subjects with the TT genotype. Moderate folate depletion in young women may cause a decrease in overall DNA methylation. The response to folate repletion suggests that following folate depletion women with the MTHFR 677 TT genotype have a greater increase in DNA methylation with folate repletion than women with the CC genotype.