Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review
- 7 July 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in The Pharmacogenomics Journal
- Vol. 9 (5), 291-305
- https://doi.org/10.1038/tpj.2009.29
Abstract
Genetic polymorphisms in the one-carbon folate pathway have been widely studied in association with a number of conditions. Most of the research has focused on the 677C>T polymorphism in the coding region of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. However, there are a total of 25 genes in this pathway coding for enzymes, transporters and receptors, which can be investigated using 267 tagging single nucleotide polymorphisms (SNPs); using SNP database (dbSNP), 38 non-synonymous SNPs with a minor allele frequency of >5% are present in these genes. Most of these variants have not been investigated in relation to disease or drug response phenotypes. In addition, their functional consequences are largely unknown. Prediction of the functional effect using six publicly available programs (PolyPhen, SIFT BLink, PMut, SNPs3D, I-Mutant2.0 and LS-SNP) was limited to functionally well-characterized SNPs such as MTHFR c.677C>T and c.1298A>C ranking low. Epigenetic modifications may also be important with some of these genes. In summary, to date, investigation of the one-carbon folate pathway genes has been limited. Future studies should aim for a more comprehensive assessment of this pathway, while further research is also required in determining the functional effects of these genetic variants.Keywords
This publication has 122 references indexed in Scilit:
- Folate Augmentation of Treatment – Evaluation for Depression (FolATED): protocol of a randomised controlled trialBMC Psychiatry, 2007
- Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: Risk of placental abruptionMolecular Genetics and Metabolism, 2007
- The methylenetetrahydrofolate reductase 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American womenNutrition Research, 2007
- Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene databaseNature Genetics, 2007
- Neural Tube Defects and Folate Pathway Genes: Family-Based Association Tests of Gene–Gene and Gene–Environment InteractionsEnvironmental Health Perspectives, 2006
- G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly populationLife Sciences, 2006
- Meta-analysis of MTHFR 677C→ T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?BMJ, 2005
- Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United StatesTeratology, 2002
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995
- Hypermethioninemia associated with methionine adenosyltransferase deficiency: Clinical, morphologic, and biochemical observations on four patientsThe Journal of Pediatrics, 1981