α1D-adrenoceptor-induced relaxation on rat carotid artery is impaired during the endothelial dysfunction evoked in the early stages of hyperhomocysteinemia

Andrade, Cláudia Roberta de; Fukada, Sandra Yasuyo; Olivon, Vânia C.; Godoy, Márcio A. F. de; Haddad, Renato; Eberlin, Marcos N.; Cunha, Fernando; Souza, Heraldo Possolo de; Laurindo, Francisco Rafael Martins; Oliveira, Ana Maria de

doi:10.1016/j.ejphar.2006.06.003

Cited by 39 publications

(63 citation statements)

References 45 publications

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“…Total plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry [6][7][8]. Hcy concentrations greater than 15 lmol/L were considered to indicate hyperhomocysteinemia [9], and MMA concentrations greater than 0.5 lmol/L defined vitamin B 12 deficiency (the conventional reference for vitamin B 12 deficiency that was used was a concentration below 200 ng/L) [8,10].…”

Section: Methodsmentioning

confidence: 99%

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

et al. 2012

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Individuals with Down syndrome (DS) carry three copies of the Cystathionine b-synthase (CbS) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.

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Section: Methodsmentioning

confidence: 99%

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

et al. 2012

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“…Plasma Hcy concentrations were determined by liquid chromatography-tandem mass spectrometry as previously described (Haddad et al, 2001;Vellasco et al, 2002;de Andrade et al, 2006), in overnight fasted mothers.…”

Section: Methodsmentioning

confidence: 99%

Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil

Biselli

Goloni-Bertollo²,

Zampieri

et al. 2008

Genet. Mol. Res.

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ABstRACt. The aim of the present study was to investigate the effect of polymorphisms C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, A2756G in methionine synthase reductase (MTR) gene and A80G in reduced folate carrier 1 (RFC1) gene, and plasma homocysteine (Hcy), on the maternal risk for Down syndrome (DS). Seventy-two DS mothers and 194 mothers who had no children with DS were evaluated. The investigation of the MTHFR C677T, MTR A2756G and RFC1 A80G polymorphisms was performed by polymerase chain reaction and enzyme digestion and the MTHFR A1298C polymorphism by allele-specific polymerase chain reaction. Hcy quantification was carried out by liquid chromatography-tandem mass spectrometry. The median number of polymorphic alleles for the four loci tested was greater in DS mothers compared to the control group, and the presence of three or more polymorphic alleles increased the risk for having a child with DS 1.74 times. Elevated maternal risk for DS was also observed when plasma Hcy concentration was higher than 4.99 µmol/L. In conclusion, the presence of three or more polymorphic alleles for MTHFR C677T, MTHFR A1298C, MTR A2756G, and RFC1 A80G, and plasma Hcy concentrations higher than 4.99 µmol/L are maternal risk factors for DS.

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“…Plasma was then stored at -80°C until assayed. Total plasma Hcy concentration was measured by mass spectrometry using the Q-TRAP, triple-quadrupole mass spectrometer (Applied Biosystems-Canada-Perkin-Elmer Sciex/QqQ-Trap, Perkin-Elmer Sciex, Thornhill, ON, Canada) using positive electrospray in multiple reaction monitoring mode with internal standard, as previously reported (20)(21)(22). Linearity of the method was r 2 = 0.9996, average of recovery 101.5% and quantification limits 1.0 µmol/L.…”

Section: Subjects and Methods Subjects And Methods Subjects And Methomentioning

confidence: 99%

The MTR A2756G polymorphism is associated with an increase of plasma homocysteine concentration in Brazilian individuals with Down syndrome

Biselli

Goloni-Bertollo

Haddad

et al. 2007

Braz J Med Biol Res

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Individuals with Down syndrome (DS) present decreased homocysteine (Hcy) concentration, reflecting a functional folate deficiency secondary to overexpression of the cystathionine ß-synthase gene. Since plasma Hcy may be influenced by genetic polymorphisms, we evaluated the influence of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR), of A2756G polymorphism in the methionine synthase gene (MTR), and of A80G polymorphism in the reduced folate carrier 1 gene on Hcy concentrations in Brazilian DS patients. Fifty-six individuals with free trisomy 21 were included in the study. Plasma Hcy concentrations were measured by liquid chromatography-tandem mass spectrometry with linear regression coefficient r 2 = 0.9996, average recovery between 92.3 to 108.3% and quantification limits of 1.0 µmol/L. Hcy concentrations >15 µmol/L were considered to characterize hyperhomocystinemia. Genotyping for the polymorphisms was carried out by polymerase chain reaction followed by enzyme digestion and allele-specific polymerase chain reaction. The mean Hcy concentration was 5.2 ± 3.3 µmol/L. There was no correlation between Hcy concentrations and age, gender or MTHFR C677T, A1298C and reduced folate carrier 1 A80G genotype. However, Hcy concentrations were significantly increased in the MTR 2756AG heterozygous genotype compared to the MTR 2756AA wild-type genotype. The present results suggest that the heterozygous genotype MTR 2756AG is associated with the increase in plasma Hcy concentrations in this group of Brazilian patients with DS.

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α1D-adrenoceptor-induced relaxation on rat carotid artery is impaired during the endothelial dysfunction evoked in the early stages of hyperhomocysteinemia

Cited by 39 publications

References 45 publications

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil

The MTR A2756G polymorphism is associated with an increase of plasma homocysteine concentration in Brazilian individuals with Down syndrome

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