Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is compelling evidence to suggest that both the development of bone to peak bone mass at maturity and subsequent loss depend on the interaction between genetic, hormonal, environmental and nutritional factors. The major part (< or = 80%) of the age-specific variation in bone turnover and bone density is genetically determined. However, the notion of genetic determinant is of little value unless the specific genes that are involved can be identified. Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (alpha and beta), apolipoprotein E, collagen type I alpha 1 and methylenetetrahydrofolate reductase, amongst many others. However, in general, findings from numerous studies of the association between such genes and various bone variables have been inconsistent. In addition to possible gene-gene interactions it is likely that there are interactions between these genes and certain environmental factors, especially nutrition, that may mediate expression of bone-related phenotypes. While these potential interactions add a level of complexity to our understanding of these apparent genetic effects on bone, identification of a role for genetic factors without knowledge of their interaction with nutrients can do little to advance prevention and treatment of osteoporosis. This information is especially important because, unlike genotype, diet and nutrition can be modified. The aim of the present review is to critically evaluate current knowledge relating to candidate genes for osteoporosis, with particular emphasis on their interaction with nutrients and dietary factors in determining bone health.
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PMID:Impact of genetic variation on metabolic response of bone to diet. 1501 90

While buccal cells provide an easily accessible source of genomic DNA, the amount extracted may be insufficient for many studies. Whole genome amplification (WGA) using multiple displacement amplification (MDA) may optimize buccal cell genomic DNA yield. We compared the usefulness, in epidemiological surveys, of DNA derived from buccal cells collected by alcohol mouthwash and amplified by WGA protocol and standard protocols. Buccal cell collection kits were mailed to 300 randomly selected members of a large cohort study, and 189 subjects returned buccal cell samples. We determined: (i) which QIAamp DNA Blood Mini Kit extraction protocol (tissue or blood) produced more DNA; and (ii) whether it is feasible to use MDA to prepare DNA for single nucleotide polymorphism (SNP) genotyping of markers such as the methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR) genes. The two DNA extraction protocols were tested on 20 different patient samples each. The tissue protocol yielded more DNA than the blood protocol (15.4+/-8.6 vs. 7.6+/-7.1 microg, p<0.0001). The 20 DNA samples extracted using the tissue protocol were then subjected to pre- and post-MDA genotyping using amplicons for the MTHFR SNP at C677T and the intron 8 VDR SNP. No genotyping discrepancies were detected in pair-wise comparisons of pre- and post-MDA. Genotyping DNA from MDA-based WGA is indistinguishable from routine polymerase chain reaction and offers a stable DNA source for genomic research and clinical diagnosis.
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PMID:Whole genome amplification of buccal cell DNA: genotyping concordance before and after multiple displacement amplification. 1584 9

Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both nutrients are implicated in skin carcinogenesis. We evaluated genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) and the vitamin D receptor (VDR) gene (Fok1, Bsm1 and Cdx2) with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC) and 873 controls]. No significant associations were observed for the two MTHFR polymorphisms on skin cancer risk. We observed an interaction between the C677T polymorphism and total folate intake on SCC risk (P, interaction=0.04); the highest risk was observed among women with TT genotype and low folate intake (OR=2.14; 95% CI=1.01-4.50). The VDR Bsm1 BB genotype was significantly associated with an increased SCC risk (OR=1.51; 95% CI=1.00-2.28). An interaction between the Bsm1 polymorphism and total vitamin D intake on SCC was observed, with the highest risk seen in women with the BB genotype and high vitamin D intake (OR=2.38; 95% CI=1.22-4.62) (P, interaction=0.08). This study suggests a possible role of the polymorphisms in MTHFR and VDR interacting with dietary intakes of folate and vitamin D in skin cancer development, especially for SCC. Due to a large number of comparisons and tests, the possible associations should be interpreted with caution and confirmed by other studies.
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PMID:Polymorphisms in the MTHFR and VDR genes and skin cancer risk. 1695 Aug

Osteoporosis is partly genetically determined. The genetics of osteoporosis is polygenic in nature with multiple common polymorphic alleles interacting with each other and environmental factors to determine bone mass. A number of studies have attempted to dissect the genetic factors responsible for the pathogenesis of osteoporosis using genome-wide scanning and the candidate gene approach. However, the results of such studies among different populations have been mostly inconsistent, suggesting genetic heterogeneity of osteoporosis. It is likely that the cohort of genes indicating predisposition to the risk of osteoporosis may be different among populations with different ethnic backgrounds. The successful identification of susceptibility genes for osteoporosis should prove to be helpful in targeting preventive and therapeutic measures to individuals at higher risk and to render the effort more cost-effective. Information with regard to genetic variations is also likely to be useful in targeting preventive or therapeutic measures to subjects genetically determined to have better responsiveness. Intestinal calcium absorption is dependent on vitamin D receptor gene polymorphisms. Skeletal responsiveness to estrogen, particularly at lower doses, is related to polymorphisms in the estrogen receptor-alpha gene. Recently, circulating homocysteine levels have been shown to be associated with fracture risk. Folate and vitamin B supplements for reducing serum homocysteine and fractures in postmenopausal women have not been fully investigated. However, there is an interaction between folate status and methylenetetrahydrofolate reductase gene polymorphism on bone phenotypes. Due to recent technological advances, whole-genome association study is becoming more feasible. Genomic information with regard to the susceptibility to osteoporosis and the responsiveness to preventive or therapeutic modalities should supplement rather than replace conventional clinical information. Clinical decision should also take into account the social, health and economic perspectives in order to balance the benefit of novel clinical strategies against the associated risks and available resources.
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PMID:Osteoporosis: the role of genetics and the environment. 1768 12

Individual differences in drug efficacy or toxicity can be influenced by genetic factors. We investigated whether polymorphisms of pharmacogenes that interfere with metabolism of drugs used in conditioning regimen and graft-versus-host disease (GvHD) prophylaxis could be associated with outcomes after HLA-identical hematopoietic stem cell transplantation (HSCT). Pharmacogenes and their polymorphisms were studied in 107 donors and patients with leukemia receiving HSCT. Candidate genes were: P450 cytochrome family (CYP2B6), glutathione-S-transferase family (GST), multidrug-resistance gene, methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR). The end points studied were oral mucositis (OM), hemorrhagic cystitis (HC), toxicity and venoocclusive disease of the liver (VOD), GvHD, transplantation-related mortality (TRM) and survival. Multivariate analyses, using death as a competing event, were performed adjusting for clinical factors. Among other clinical and genetic factors, polymorphisms of CYP2B6 genes that interfere with cyclophosphamide metabolism were associated with OM (recipient CYP2B6(*)4; P=0.0067), HC (recipient CYP2B6(*)2; P=0.03) and VOD (donor CYP2B6(*)6; P=0.03). Recipient MTHFR polymorphisms (C677T) were associated with acute GvHD (P=0.03), and recipient VDR TaqI with TRM and overall survival (P=0.006 and P=0.04, respectively).Genetic factors that interfere with drug metabolisms are associated with treatment-related toxicities, GvHD and survival after HLA-identical HSCT in patients with leukemia and should be investigated prospectively.
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PMID:Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia. 1900 82

In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case-control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.
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PMID:Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk. 3124 14