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Plasma Homocysteine Concentration (plasma + homocysteine_concentration)
Selected AbstractsG1793A polymorphisms in the methyl- enetetrahydrofolate gene: Effect of folic acid on homocysteine levelsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2006Sandra Soares Melo Abstract Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program , Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B12 by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B12 deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = ,0.27, p = 0.01) and vitamin B12 (r = ,0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B12 concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation. [source] Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wallEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002P. Hämelahti Abstract Background The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. Materials and methods The autopsy study included 123 subjects (90 males and 33 females) aged 18,93. For the light microscopy, a 0·5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. Results The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2·02 ± 2·25 vs. 2·53 ± 1·89, P < 0·04 and 0·56 ± 1·09 vs. 1·82 ± 2·66, P < 0·02, respectively). The trend was similar for the coeliac and the right renal arteries. Conclusions Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL. [source] Effect of bezafibrate on plasma homocysteine concentration in men with lower extremity arterial diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2004P. K. MacCallum No abstract is available for this article. [source] The Effect of Glutathione Modulation on the Concentration of Homocysteine in Plasma of RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2000Kjell K. Øvrebø Elevated plasma homocysteine concentration in humans is associated with increased risk of arteriosclerosis and ischaemic heart disease. We studied whether the plasma homocysteine concentration could be changed by administration of drugs that modulate the concentration of glutathione in both plasma and tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg), N -acetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min. later an arterial blood sample was drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The total homocysteine concentration in plasma of fasted rats was 6.1±0.5 ,M. Intravenous administration of reduced glutathione or N -acetylcysteine reduced the homocysteine concentration in plasma significantly by 51% to 3.0±0.3 ,M and 63% to 2.2±0.2 ,M, respectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased the concentration of homocysteine by 41% to 8.6±0.6 ,M (P<0.05). The glutathione concentration in plasma was 19.5±1.9 ,M in controls and was unchanged by N -acetylcysteine administration. Reduced glutathione increased plasma glutathione to 379.7±22.9 ,M (P<0.05), whereas L-buthionine-[S R]-sulfoximine lowered the plasma glutathione concentration to 5.3±0.4 ,M. Homocysteine was negatively correlated to the glutathione (r=,0.399, P<0.01) and the cysteine (r=,0.52, P<0.01) concentrations in plasma. Our conclusion is that modulation of the glutathione levels influences the concentration of homocysteine in plasma of rats. [source] Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentrationCLINICAL GENETICS, Issue 6 2004J Wang Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine ,-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations. [source] Epigenetic DNA Hypermethylation of the HERP Gene Promoter Induces Down-regulation of Its mRNA Expression in Patients With Alcohol DependenceALCOHOLISM, Issue 4 2006Stefan Bleich Background: Elevated plasma homocysteine concentrations can influence genomic and gene-specific DNA methylation in peripheral blood cells. The aim of this study was to investigate in patients with alcohol dependence, who show chronically elevated homocysteine levels, whether DNA methylation pattern within the HERP (homocysteine-induced endoplasmic reticulum protein) promoter region and expression of HERP mRNA is altered. Methods: The HERP mRNA expression level was measured by quantitative PCR in the blood of 66 male alcoholic patients and 55 nondrinking healthy controls. Epigenetic genomic DNA methylation status and HERP promoter methylation were measured with a nonradioactive elongation assay. Results: We observed a significant increase (7.6%) in the HERP promoter DNA methylation in patients with alcohol dependence (t test, t=,2.45, p<0.02) when compared with healthy controls (80.4%, SD 14.5), which was significantly associated with their elevated homocysteine levels (multiple linear regression, p<0.007). Furthermore, we found a significantly lower HERP mRNA expression in patients with alcohol dependence (t test, ,7.61 ,CT; SD 1.87, p<0.001) when compared with healthy controls (,6.04 ,CT; SD 2.41). The lowered HERP mRNA expression in alcoholic patients was best explained by the hypermethylation of the regulatory HERP gene promoter (regression analysis, p=0.004). Conclusions: To our knowledge, this is the first study evaluating HERP mRNA expression and its specific gene promoter methylation in alcoholic patients. As hypermethylation of DNA is an important epigenetic factor in the down-regulation of gene expression, and as HERP has been considered to play an essential role within the intracellular defense system, these findings may be useful in the understanding and treatment of different disease conditions associated with alcohol dependence. [source] G1793A polymorphisms in the methyl- enetetrahydrofolate gene: Effect of folic acid on homocysteine levelsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2006Sandra Soares Melo Abstract Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program , Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B12 by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B12 deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = ,0.27, p = 0.01) and vitamin B12 (r = ,0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B12 concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation. [source] Endothelial markers and homocysteine in patients with classic Fabry diseaseACTA PAEDIATRICA, Issue 2002K Demuth Aim: Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of ,-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT). Methods: Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT. Results: Compared with the controls, plasma concentrations of homocysteine were significantly (p > 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly (p > 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls. Conclusions: The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present. [source] | |||||||||||||