Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy

• Published in: Molecular genetics and metabolism Vol. 81; no. 4; pp. 273 - 281
• Main Authors: Relton, Caroline L, Wilding, Craig S, Laffling, Alison J, Jonas, Pat A, Burgess, Terry, Binks, Keith, Janet Tawn, E, Burn, John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2004
• Subjects: Adult; Case-Control Studies; Erythrocytes - metabolism; Female; Folate; Folic Acid - blood; Folic Acid - genetics; Folic Acid Deficiency - genetics; Humans; Neural tube defect; Neural Tube Defects - etiology; Neural Tube Defects - genetics; Polymorphism; Polymorphism, Genetic; Pregnancy; Pregnancy Complications; Risk Factors; Neural tube defect; Folate; Polymorphism
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2003.12.010

Previous studies have shown conflicting findings in linking polymorphic variation in folate-related genes to the risk of neural tube defect pregnancy. Recent evidence points to maternal genotype being important in determining NTD risk. A case-control study was undertaken in 97 mothers of NTD cases from the northern region of the UK. Pregnant controls ( n=190) from a regional DNA bank and non-pregnant controls ( n=100) from the same geographical area were recruited. MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, SHMT 1420C>T, CβS 844ins68, and RFC-1 80G>A allele and genotype frequencies were determined and odds ratios (OR) calculated. Erythrocyte folate levels for cases and controls were also measured and a comparison made of median erythrocyte folate levels stratified according to genotype. The MTHFR 677C>T variant was not shown to be an independent NTD risk factor in mothers of NTD-affected pregnancy. A second polymorphism in MTHFR, 1298A>C, was less frequently observed in mothers of NTD cases (OR [95% CI]=0.57 [0.33, 0.97]). Possession of compound 1298A>C and 677C>T variants elevated risk of NTD pregnancy considerably (TT/AC + TT/CC vs CC/AA OR [95% CI]=6.56 [1.10, 39.33]). Erythrocyte folate levels were persistently lower in NTD mothers ( p=0.001) despite assays being conducted many years after the index pregnancy (17.6 ± 12.6 years). Erythrocyte folate levels were depressed in the presence of the MTHFR 677C>T variant.