Homocysteine levels – before and after methionine loading – in 51 Dutch families

Heijer, Martin den; Graafsma, S.J.; Lee, Soon Young; Landeghem, Bart van; Kluijtmans, Leo A. J.; Verhoef, Petra; Beaty, Terri H.; Blom, Henk J.

doi:10.1038/sj.ejhg.5201389

Cited by 14 publications

(11 citation statements)

References 23 publications

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“…However, we did not observe a similar relationship in the presence of Hcy alone (50 μM). Our observation is in line with Den Heijer's et al study, which showed that the postload homocysteine levels had stronger genetic determination than the fasting homocysteine levels [23]. In addition, current data suggests that MP number may be genetically regulated [12].…”

Section: Discussionsupporting

confidence: 92%

Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro

Sekuła

Janawa

Stankiewicz

et al. 2011

Cellular and Molecular Biology Letters

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Microparticles (MPs) are small membrane vesicles released by stimulated or apoptotic cells, including the endothelium. Hyperhomocysteinemia (HHcy) is a blood disorder characterized by an increase in the plasma concentrations of total homocysteine (Hcy). The plasma Hcy level is determined by environmental factors (dietary habits, i.e. the intake of folic acid, FA) and genetic factors (N 5,N 10-methylenetetrahydro-folate reductase, MTHFR, polymorphism 677C>T). To evaluate whether moderate Hcy concentrations induce endothelial MP formation, the role of FA supplementation and the influence of MTHFR polymorphism were analysed. Human umbilical vein endothelial cells (HUVEC) were treated in vitro with 50 μM of Hcy and methionine (Met). The MP number and apoptotic phenotype were analyzed using flow cytometry. Increasing doses of FA (5, 15 and 50 μM) were used to reduce the HHcy effect. The MTHFR 677C>T polymorphism was determined. HUVEC stimulated by Hcy produced significantly more MPs than HUVEC under the control conditions: 3,551 ± 620 vs 2,270 ± 657 kMP (p = 0.02). Supplementation with FA at concentrations of 5, 15 and 50 μM reduced the MP count in the cell culture supernatant to 345 ± 332, 873 ± 329, and 688 ± 453 kMP, respectively (p = 0.03). MTHFR 677C>T heterozygosity was associated with a significant increase in MP formation after stimulation with Hcy compared to the control conditions: 3,617 ± 152 vs 1,518 ± 343 kMP (p = 0.02). Furthermore, the MTHFR genotype altered MP formation after Met loading. On average, 24% of the entire MP population was apoptotic (annexin V-positive). Endothelial function impairment due to HHcy is related to MP shedding, which may involve platelets and other blood and vascular cells. MP shedding is a physiological response to moderate HHcy.

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Section: Discussionsupporting

confidence: 92%

Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro

Sekuła

Janawa

Stankiewicz

et al. 2011

Cellular and Molecular Biology Letters

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“…12,29,30 Souto et al 29 found modest heritability for homocysteine levels (0.24) in 21 Spanish pedigrees ascertained on the basis of thrombophilia. Jee et al 12 found a heritability of 0.47 for homocysteine levels in 661 family members of 112 probands who underwent elective Chr indicates chromosome.…”

Section: Discussionmentioning

confidence: 99%

Novel Genomic Loci Influencing Plasma Homocysteine Levels

Kullo

Ding

Boerwinkle

et al. 2006

Stroke

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Background and Purpose-Genetic factors that influence interindividual variation in levels of plasma homocysteine, a risk factor for vascular disease, are not fully understood. We performed linkage analyses to identify genomic regions that influence homocysteine levels in blacks and non-Hispanic whites. Methods-Subjects (nϭ2283) belonged to hypertensive sibships and included 1319 blacks (63Ϯ10 years, 70% women) and 964 non-Hispanic whites (61Ϯ7 years, 57% women). Fasting plasma homocysteine was measured by high-pressure liquid chromatography. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Plasma homocysteine adjusted for age, sex, body mass index, serum creatinine, and estrogen use (in women) was used in the genetic analyses. Heritability and linkage analyses were performed using a variance components approach. Results-Mean (ϮSD) homocysteine levels were 10.4Ϯ5.27 mol/L in blacks and 10.0Ϯ2.84 mol/L in non-Hispanic whites (Pϭ0.58 for difference). Homocysteine levels were significantly (PϽ0.0001) heritable in blacks (h 2 ϭ0.70) and in non-Hispanic whites (h

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“…The strong homocysteine-lowering effect of folate supplementation 46 indicates that this form of dysfunctional folate metabolism can be overcome by additional folate intake. Because homocysteine concentrations are to a large extent under genetic control 47,48 , homocysteine can be used as a biomarker to detect human NTD candidate genes that are involved in storage, transport and metabolism of folate. The identification of such genetic variants will also contribute to our understanding of the mechanisms underlying the role of folate in the prevention of NTDs.…”

Section: Genetic Variation In Folate Metabolismmentioning

confidence: 99%

Neural tube defects and folate: case far from closed

Shaw²,

et al. 2006

Self Cite

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Neural tube closure takes place during early embryogenesis and requires interactions between genetic and environmental factors. Failure of neural tube closure is a common congenital malformation that results in morbidity and mortality. A major clinical achievement has been the use of periconceptional folic acid supplements, which prevents ~50-75% of cases of neural tube defects. However, the mechanism underlying the beneficial effects of folic acid is far from clear. Biochemical, genetic and epidemiological observations have led to the development of the methylation hypothesis, which suggests that folic acid prevents neural tube defects by stimulating cellular methylation reactions. Exploring the methylation hypothesis could direct us towards additional strategies to prevent neural tube defects.Neural tube defects (NTDs) are complex congenital malformations of the CNS. Anencephaly and spina bifida are the most common and severe forms of NTD, with a prevalence of about 1 in 1,000 births, although this varies throughout the world 1 . Infants with anencephaly are stillborn or die shortly after birth, whereas infants with spina bifida can survive but are likely to have severe lifelong disabilities and are at risk of psychosocial maladjustment. The estimated lifetime medical costs are high; for example, in California, USA, the costs for children born with spina bifida exceed US$81 million per year 2 .It has been known for more than 20 years that women can reduce their risk of having an NTDaffected pregnancy by taking folic acid supplements. However, the underlying mechanisms byCorrespondence to H.J.B. H.Blom@cukz.umcn.nl. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Neurosci. Author manuscript; available in PMC 2010 November 2. Neurulation and neural tube defectsNeurulation has long fascinated scientists, as evidenced by a devoted literature that extends back hundreds of years. The process of neurulation occurs during early embryogenesis, starting with the formation of the neural plate from specialized ectodermal cells and culminating in the closure of the neural tube (FIG. 1), the precursor of both the CNS and most of the PNS. Considered most simply, the neural plate develops bilateral neural folds, which elevate and fuse at the midline to create the neural tube. Subsequent development, together with vesiculation within the tube, gives rise to the brain and spinal cord. Further details of this complex process are beyond the scope of this review (for reviews, see REFS 4,5 ).Neurulation seems to be highly complex and tightly regulated. The development and closure of the neural tube is usually completed by 28 days post-conception. This means that by the time a woman finds out that she is pregnant, the neural tube is almost completely closed. For the neural tube to close properly, genes that regulate various morphogenetic activities must function cooperatively. These activities include programmed cell death, neural crest...

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Homocysteine levels – before and after methionine loading – in 51 Dutch families

Cited by 14 publications

References 23 publications

Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro

Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro

Novel Genomic Loci Influencing Plasma Homocysteine Levels

Neural tube defects and folate: case far from closed

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