Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study

Kirke, Peadar N.; Mills, James L.; Molloy, Anne M.; Brody, Lawrence C.; O’Leary, Valerie B.; Daly, Leslie; Murray, Sharon C.; Conley, Mary; Mayne, Philip; Smith, O. O.; Scott, John M.

doi:10.1136/bmj.38036.646030.ee

Cited by 116 publications

(99 citation statements)

References 6 publications

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“…The ability to identify those who are more susceptible to having NTD-affected pregnancies -the object of some studies [43][44][45] -is an exciting challenge and may enable targeted programs to be developed, obviating the need for whole population strategies.…”

Section: Food Folate and Physical Activitymentioning

confidence: 99%

Use of periconceptional folic acid supplements in Victoria and New South Wales, Australia

Watson

Brown

Davey

2006

Australian and New Zealand Journal of Public Health

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In both surveys younger women, women with less education, less income, of nonEnglish speaking background and women who were not married were less likely to take folate supplements in the recommended period. In Victoria, multiparous women were significantly less likely to take supplements. In NSW, women with an unplanned pregnancy and those living in rural areas were significantly less likely to take periconceptional folate supplements. Fifty-three per cent of women cited a general practitioner or obstetrician as a source of folate information and 45% cited family or friends; both of these sources were significantly associated with periconceptional folate supplementation. Conclusions: Less than 50% of women took periconceptional folate supplements.Among socially disadvantaged groups, the proportion was significantly lower. Implications: Since women are unlikely to achieve adequate folate intake periconceptionally without deliberate action, there remains the need for a multifaceted approach to providing women with information about folate. Future surveys are needed to monitor usage and knowledge. (Aust N Z J Public Health 2006; 30: 42-9) N eural tube defects (NTDs) are a group of serious congenital structural abnormalities of the brain, skull, and spinal cord that are able to be detected antenatally by the use of ultrasound and maternal serum screening in the second trimester. 1 Since the routine introduction of these tests in Victoria, the birth prevalence of NTDs has reduced because pregnancies found to be affected are usually terminated. 2,3 There are also indications that since 1997, when folate awareness programs were introduced and after voluntary fortification of folate to staple foods was recommended, 4 the incidence of NTDs including pregnancies terminated after prenatal diagnosis has decreased in Victoria. 2 These data are not available for New South Wales (NSW).There is strong evidence that an adequate intake of folate periconceptionally reduces the risk of NTDs by about two-thirds, 5 and that folate (or folic acid) is only effective in reducing the risk of NTDs when recommended maternal folate levels are achieved before the critical time that neural tube closure occurs, around week four after conception. The National Health and Medical Research Council 6 has recommended that "women planning a pregnancy or likely to become pregnant should be encouraged to increase their dietary intake of folate-rich foods, particularly in the month before and in the first three months of the pregnancy. Low risk women . . . should be offered periconceptional folic acid supplementation (0.5 mg daily)." NHMRC draft documentation has this amount as 400 µg/ day, in line with overseas recommendations. The current habitual dietary intake of folate for most Australian women is well below that recommended for risk reduction of NTDs. 8,9 Primary prevention strategies to reduce the risk of NTDs include: periconceptional intake of folic acid supplements, increased consumption of foods naturally high in folate, and fortification ...

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Section: Food Folate and Physical Activitymentioning

confidence: 99%

Use of periconceptional folic acid supplements in Victoria and New South Wales, Australia

Watson

Brown

Davey

2006

Australian and New Zealand Journal of Public Health

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“…Recent studies have shown that approximately 50% of the Irish population have variations in the gene coding for an enzyme involved in folate metabolism, 5,10-methylenetetrahydrofolate reductase (7)(8)(9) . Such genetic variations may account for £26 % of NTDaffected births in Ireland (10) . The situation in other countries is different in that the overall incidence of NTD is lower and most of the affected pregnancies are terminated.…”

mentioning

confidence: 99%

Session 1: Public health nutrition Folic acid food fortification: the Irish experience

et al. 2008

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Adequate intake of folic acid by women during very early pregnancy can markedly reduce risk of the development of neural-tube defects (NTD). The effectiveness of advice to women to take folic acid supplements is limited, mainly because 50 % of pregnancies are unplanned. However, mandatory folic acid food fortification programmes in North America have been very successful in reducing NTD rates. In Ireland higher rates of pregnancies are affected by NTD and the option of termination is illegal. Consequently, the much higher burden of disease makes primary prevention of NTD an important public health issue in Ireland. During 2006 a decision was taken in Ireland to initiate mandatory folic acid fortification of most bread to prevent NTD. Priority work was immediately undertaken to establish reliable and comprehensive baseline information on factors that will be affected by fortification. This information included data on: the national prevalence of pregnancies affected by NTD; the current extent of voluntary folic acid fortification of food on the Irish market and how it affects folic acid intakes; blood folate status indicators assessed for various subgroups of the Irish population. In addition, scientific developments that have arisen since 2006 relating to the risks and benefits of folic acid intake are under ongoing review. The present paper summarises the rationale for mandatory folic acid food fortification in Ireland and recent scientific developments relating to risks and benefits of folic acid intake. In this context, preliminary findings of baseline monitoring investigations in Ireland are considered.

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“…Clearly, half the population are not born with an NTD. The real prevalence rate for NTD has dropped from a high of seven per 1000 births to about one per 1000 births (14) . Clearly, many of these children will be heterozygous for the variant and a substantial minority will be homozygous for the variant (15) .…”

Section: Neural-tube Defectsmentioning

confidence: 99%

“…The variant is very common in the Irish population and those of European origin, with a widely different prevalence worldwide. The prevalence of being homozygous or heterozygous for the variant is approximately 10% and 40% respectively (14) . Thus, over half the population have at least one flawed copy of this variant and thus in turn so does every child born in the country.…”

Section: Neural-tube Defectsmentioning

confidence: 99%

“…C677T polymorphism for the enzyme 5,10-methylenetetrahydrofolate reductase, makes a small but important contribution to the explanation of a birth that is affected by spina bifida or another NTD, which is described as the population attributable risk (14) . The variant is very common in the Irish population and those of European origin, with a widely different prevalence worldwide.…”

Section: Neural-tube Defectsmentioning

confidence: 99%

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Session 2: Personalised nutrition Genetic variation and disease risk: new advances

Scott

2009

Proc. Nutr. Soc.

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Variations in human DNA, most frequently single-nucleotide polymorphisms (SNPs), can have functional consequences ranging from severe to none. Variations in outcome (phenotype) can be compared, from cystic fibrosis through haemochromatosis to general familial risks in, for example, colo-rectal cancer (CRC). Cystic fibrosis and haemochromatosis have severe phenotypes with high penetrance, with signs and symptoms always or mostly present; thus, they have been easy to identify from family studies. However, the familial risks that are known to contribute markedly to CRC are unknown. The sequencing of the human genome has now made possible the identification of these and other disease variants. Knowing the DNA sequence in an idealised individual adds little unless variants that increase (or decrease) disease risk from the norm can be identified. Such variants can be expected to be very common in the general population, but have low penetrance and only change risk to a limited extent. Many patients will not have the risk variant and many ‘normal’ patients will have the risk variant. Thus, very large case–control cohorts are essential. These case–control cohorts can be analysed at three different levels: (1) individual SNPs; (2) individual genes; (3) genome-wide analysis (GWA). Level 1 looks for case–control differences for specific SNPs. Alternatively, new technology can be applied to examine a range of SNPs within a gene to track differences in its regulation as well as in function. Finally, the whole genome with ≥0·5×106 SNPs could be marked. The first two approaches involve selecting ‘candidate’ SNPs or genes, while GWA looks for any variation in the genome that is enriched in the cases. All three approaches carry the certainty that significant associations will be found by statistical chance, for which correction must be made. This latter issue is helped by large numbers and by independent replication cohorts.

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Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study

Cited by 116 publications

References 6 publications

Use of periconceptional folic acid supplements in Victoria and New South Wales, Australia

Use of periconceptional folic acid supplements in Victoria and New South Wales, Australia

Session 1: Public health nutrition Folic acid food fortification: the Irish experience

Session 2: Personalised nutrition Genetic variation and disease risk: new advances

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