Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

Christensen, Benedicte; Arbour, Laura; Tran, Pamela V.; Leclerc, Daniel; Sabbaghian, Nelly; Platt, Robert W.; Gilfix, Brian M.; Rosenblatt, David S.; Gravel, Roy A.; Forbes, Patricia A.; Rozen, Rima

doi:10.1002/(sici)1096-8628(19990521)84:2<151::aid-ajmg12>3.3.co;2-k

Cited by 44 publications

(62 citation statements)

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“…Unfortunately, no nutrition inquiry was performed. Normal levels of serum folate have been reported by several studies (Christensen et al, 1999; Villarreal et al, 2001). The level of folate is probably not associated with NTDs in our population, which is different from findings by other authors (Gardiki‐Kouidou and Seller, 1988; Wild et al, 1994).…”

Section: Discussionmentioning

confidence: 72%

“…Further studies focusing on the genetic analysis of the genes involved in homocysteine methionine metabolism are needed. An enzyme, methionine synthase, is also associated with homocysteine metabolism, and a polymorphism, a 2756A>G mutation, has been identified (Leclerc et al, 1996), but several studies have failed to demonstrate any association of this polymorphism with NTDs (Van der Put et al, 1997; Morrison et al, 1998; Christensen et al, 1999). Another enzyme, methionine synthase reductase, which is responsible for maintaining the methionine synthase in its active state, has recently been cloned (Leclerc et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

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Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil

Félix

Leistner

Giugliani

2004

Birth Defects Research

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil

Félix

Leistner

Giugliani

2004

Birth Defects Research

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“…These authors have speculated that maternal effects could reflect epigenetic processes like imprinting or maternal genotype effects in the intrauterine environment. Maternal effects have been described for other birth defects, particularly when gene–nutrient interactions are present [Christensen et al, 1999], such as the case of the maternal MTHFR genotype effect in the risk of NSCLP [Martinelli et al, 2001; Prescott et al, 2002; Jugessur et al, 2003; van Rooij et al, 2003]. Nevertheless, no epigenetic control has yet been demonstrated for NSCLP candidate genes.…”

Section: Discussionmentioning

confidence: 99%

Parent‐of‐origin effects for MSX1 in a Chilean population with nonsyndromic cleft lip/palate

Suazo

Santos

Jara

et al. 2010

American J of Med Genetics Pt A

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Based on association and sequencing studies, investigators have postulated muscle segment homeobox 1 (MSX1) as a strong candidate gene involved in the causation of nonsyndromic cleft lip with or without cleft palate (NSCLP). Parent-of-origin effects have been suggested for some NSCLP candidate genes but not for MSX1. The aims of the present study were to test for allele/haplotype associations applying the transmission disequilibrium test (TDT) and the transmission asymmetry test (TAT) to evaluate the possible parent-of-origin effects of MSX1 in Chilean patients with NSCLP. We analyzed five SNPs (rs6446693/c.-425G>T/c.-35G>A/rs3775261/rs12532) located from 6.3 kb upstream to 3' UTR in a sample of 150 unrelated NSCLP case-parent trios. Four haplotypes showed overtransmission from parents to affected progeny, but individual SNPs did not. Two haplotypes presented allele combination C-G-A-G (P = 0.035) and two T-G-C-A (P = 0.044) (SNP order rs6446693/c.-35G>A/rs3775261/rs12532). The rs12532 A allele had a 2.08-fold increase in the risk of NSCLP when inherited from the father (95% CI: 1.10-4.02; P = 0.025), but not from the mother. These results could indicate epigenetic control by imprinting in the role of MSX1 in NSCLP. Different authors have proposed that some genes that play a role in NSCLP depend on parental origin. Our findings and those previously reported by our group show that a variety of factors appears to be involved in the association between MSX1 and NSCLP. The full mechanism of MSX1 in the development of NSCLP has not been fully understood.

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“…These findings have led to the hypothesis that genetic defects in folate metabolism or transport may account for variations in individual susceptibility to NTD‐affected pregnancies. However, although some gene polymorphisms in folate transporters and folate‐pathway enzymes have been identified (Christensen et al, ; Beaudin and Stover, ), studies to date have provided no conclusive evidence that these genetic differences affect folate status (Beaudin and Stover, ). Together, these results highlight that folic acid appears to be a corrective, rather than causal factor, in the etiopathogenesis of NTDs (Wallingford et al, ).…”

Section: Introductionmentioning

confidence: 99%

Neural tube defects, folate, and immune modulation

Denny

Jeanes

Fathe

et al. 2013

Birth Defects Research

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Periconceptional supplementation with folic acid has led to a significant worldwide reduction in the incidence of neural tube defects (NTDs). However, despite increasing awareness of the benefits of folic acid supplementation and the implementation of food fortification programs in many countries, NTDs continue to be a leading cause of perinatal morbidity and mortality worldwide. Furthermore, there exists a significant subgroup of women who appear to be resistant to the protective effects of folic acid supplementation. The following review addresses emerging clinical and experimental evidence for a role of the immune system in the etiopathogenesis of NTDs, with the aim of developing novel preventative strategies to further reduce the incidence of NTD-affected pregnancies. In particular, recent studies demonstrating novel roles and interactions between innate immune factors such as the complement cascade, neurulation, and folate metabolism are explored.

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Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

Cited by 44 publications

References 0 publications

Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil

Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil

Parent‐of‐origin effects for MSX1 in a Chilean population with nonsyndromic cleft lip/palate

Neural tube defects, folate, and immune modulation

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