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 considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.
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PMID:Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease. 1143 25

The following seven polymorphic marker loci of genes responsible for predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus responsible for angiotensin-converting enzyme insertion/deletion polymorphism for the presence or absence of the Alu insertion in the gene; the F13, PLAT, and APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci responsible for point mutations in methylenetetrahydrofolate reductase and those in angiotensinogen, respectively, and the NOS3 locus controlling the number of tandem repeats in the nitric oxide synthase gene. These loci are located on different chromosomes and encode products involved into various metabolic pathways leading to CAS. In the populations studied, significant differences between healthy subjects and patients predisposed to cardiovascular diseases were revealed with regard to the above seven markers. The 174M allele (T174M polymorphism in the ACE gene) was significantly associated with coronary atherosclerosis. It was found that specific gene combinations are involved in the CAS development and determine variation in the pathogenetically important quantitative traits.
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PMID:[Analysis of gene complexes predisposing to coronary atherosclerosis]. 1196 67

Elevated homocysteine is a risk marker for several human pathologies. Risk factors for elevated homocysteine include low folate and homozygosity for the T allele of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Because nitric oxide may inhibit folate catabolism and endothelial nitric oxide synthase activity is reduced in smokers, we postulated that smoking status might modify the impact of the MTHFR C677T polymorphism on homocysteine (tHcy) concentrations. We tested this hypothesis in a healthy young adult population for which MTHFR C677T genotypes and tHcy concentrations were previously reported. The MTHFR 677TT genotype was significantly associated with elevated tHcy concentrations in smokers (P = 0.001) but not in non-smokers (P = 0.36). Among smokers, the MTHFR 677TT genotype was significantly associated with high tHcy in heavy smokers (P = 0.003) but not light smokers (P = 0.09), in men (P = 0.003) but not women (P = 0.11), and in subjects from the lowest serum folate quartile (P = 0.49) but not from folate quartiles 2-4 (P = 0.49). After adjustment for nutritional variables, interactions between MTHFR C677T genotype and NOS3 G894T genotype, and between MTHFR genotype, smoking status and gender were statistically significant. We propose that hyperhomocysteinemia in MTHFR 677TT homozygote smokers is the consequence of mild intracellular folate deficiency caused by a smoking-related reduction of NOS3 activity that is exacerbated when serum folate is low.
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PMID:The 5,10-methylenetetrahydrofolate reductase C677T polymorphism interacts with smoking to increase homocysteine. 1513 61

Vascular access thrombosis (VAT) remains a significant problem worldwide. This study determined the association between VAT and 7 candidate gene polymorphisms (factor V Leiden 1691G>A, factor II 20210G>A, methylenetetrahydrofolate reductase 677C>T, angiotensin converting enzyme 287 base pair (bp) insertion/deletion, transforming growth factor-beta1 869T>C and 915G>C, NOS3 -786T>C and intron 4 27 bp tandem repeat, and endotoxin receptor CD14 -159C>T). This was a retrospective case-control pilot study conducted in 101 hemodialysis patients at a large tertiary-care, University health-science center. Sixty cases that experienced frequent VAT and 41 controls that had not experienced VAT in at least 3 years were evaluated for demographics and genotyping. These data were summarized, and univariable and multivariable regression models were constructed. Univariate VAT predictors included the NOS3 420 bp allele (P=0.03) and the presence of a central venous dialysis catheter (P<0.01). Aspirin use was protective against VAT (P=0.02). In the multivariate analysis, the dialysis access type remained a significant predictor of thrombosis (P<0.01), while aspirin use retained its protective status (P=0.01). Statin use was associated with the cases (P=0.02); however, the NOS3 420 bp allele failed to improve the model. These data confirm that central venous dialysis catheter access is associated with thrombosis, while aspirin use appears protective. The NOS3 420 bp allele may have an association with thrombosis; however, further epidemiologic data evaluating large dialysis registries are needed to confirm our observation.
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PMID:A pilot study of genetic polymorphisms and hemodialysis vascular access thrombosis. 1921 Feb 73