Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study
http://www.100md.com
《英国医生杂志》
1 Child Health Epidemiology Division, Health Research Board, Dublin 2, Ireland, 2 Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MA 20892, USA, 3 Department of Clinical Medicine, Trinity College Dublin, St James's Hospital, Dublin 8, 4 Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, 5 Department of Biochemistry, Trinity College Dublin, Dublin 2, 6 Department of Public Health Medicine and Epidemiology, University College Dublin, National University of Ireland, Dublin 2, 7 The Children's University Hospital, Dublin 1, 8 National Centre for Hereditary Coagulation Disorders, St James's Hospital, Dublin 8
Correspondence to: P N Kirke pkirke@hrb.ie
Introduction
We recruited 397 individuals with spina bifida aperta (380) or encephalocele (17) throughout Ireland. Participants were aged between 5 months and 52 years (mean 16.8 years). We drew blood for analysis of DNA. We derived the controls from a random sample of 1000 newborn screening cards collected on all Irish births. Of these 1000, DNA was successfully extracted from 855 cards. We successfully genotyped 395 (99.5%) cases and 848 (99.2%) controls.
We calculated population attributable fractions, broadly interpreted as the percentage of the disease in a population that is "caused by" a risk factor, for heterozygotes and homozygotes separately comparing each to the wild type.
The heterozygous genotype is associated with an increased risk of neural tube defects (odds ratio 1.52; P = 0.0015; table). Risk is also raised for the homozygous TT genotype (2.56; P < 0.0001), confirming our earlier finding.3
Risk of neural tube defect by the 5,10-methylenetetrahydrofolate reductase C677T genotype
Population attributable fraction calculations reveal that the CT genotype is responsible for at least as many neural tube defects in the population as the TT genotype (14.9% 11.3%; table). This arises because a much greater proportion of the population are heterozygous for this allele (about 38% of the general population are CT compared with 10% who are TT; table).
Comment
Botto LD, Yang Q. 5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000;151: 862-77.
Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, et al. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 1995;345: 149-51.
Shields DC, Kirke PN, Mills JL, Ramsbottom D, Molloy AM, Burke H, et al. The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: an evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother. Am J Hum Genet 1999;64: 1045-55.
Johanning GL, Tamura T, Johnston KE, Wenstrom, KD. Comorbidity of 5,10-methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms and risk for neural tube defects. J Med Genet 2000;37: 949-51.
Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325: 1202-8.(Peadar N Kirke, specialis)
Correspondence to: P N Kirke pkirke@hrb.ie
Introduction
We recruited 397 individuals with spina bifida aperta (380) or encephalocele (17) throughout Ireland. Participants were aged between 5 months and 52 years (mean 16.8 years). We drew blood for analysis of DNA. We derived the controls from a random sample of 1000 newborn screening cards collected on all Irish births. Of these 1000, DNA was successfully extracted from 855 cards. We successfully genotyped 395 (99.5%) cases and 848 (99.2%) controls.
We calculated population attributable fractions, broadly interpreted as the percentage of the disease in a population that is "caused by" a risk factor, for heterozygotes and homozygotes separately comparing each to the wild type.
The heterozygous genotype is associated with an increased risk of neural tube defects (odds ratio 1.52; P = 0.0015; table). Risk is also raised for the homozygous TT genotype (2.56; P < 0.0001), confirming our earlier finding.3
Risk of neural tube defect by the 5,10-methylenetetrahydrofolate reductase C677T genotype
Population attributable fraction calculations reveal that the CT genotype is responsible for at least as many neural tube defects in the population as the TT genotype (14.9% 11.3%; table). This arises because a much greater proportion of the population are heterozygous for this allele (about 38% of the general population are CT compared with 10% who are TT; table).
Comment
Botto LD, Yang Q. 5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000;151: 862-77.
Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, et al. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 1995;345: 149-51.
Shields DC, Kirke PN, Mills JL, Ramsbottom D, Molloy AM, Burke H, et al. The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: an evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother. Am J Hum Genet 1999;64: 1045-55.
Johanning GL, Tamura T, Johnston KE, Wenstrom, KD. Comorbidity of 5,10-methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms and risk for neural tube defects. J Med Genet 2000;37: 949-51.
Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325: 1202-8.(Peadar N Kirke, specialis)