title: Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy.
abstract: 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, CbetaS 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.
authors.affiliation: Paediatric and Lifecourse Epidemiology Research Group, School of Clinical Medical Sciences (Child Health), Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne NE2 4LP, UK. caroline.relton@westlakes.ac.uk
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.forename: Craig S
authors.initials: CS
authors.lastname: Wilding
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Laffling
authors.forename: Pat A
authors.initials: PA
authors.lastname: Jonas
authors.forename: Terry
authors.initials: T
authors.lastname: Burgess
authors.forename: Keith
authors.initials: K
authors.lastname: Binks
authors.forename: E Janet
authors.initials: EJ
authors.lastname: Tawn
authors.forename: John
authors.initials: J
authors.lastname: Burn
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000235:genetics*; D005494:Folic Acid Deficiency / Q000235:genetics*; D006801:Humans; D009436:Neural Tube Defects / Q000209:etiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications; D012307:Risk Factors
chemical_list: D005492:Folic Acid