Homocysteine Concentrations and Molecular Analysis in Patients with Congenital Heart Defects

Galdieri, Luciano; Arrieta, Santiago Raul; Silva, Célia M.C.; Pedra, Carlos A. C.; D’Almeida, Vânia

doi:10.1016/j.arcmed.2006.09.012

Cited by 32 publications

(36 citation statements)

References 35 publications

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“…Homocysteine has been recognized as an embryoteratogenic agent associated with congenital heart defects, although this is still controversial [12,26]. In the current study, homocysteine was administered on GD 8, 9, and 10, which is the time period during which the heart tube transforms into the rudimentary heart in the fetus.…”

Section: Discussionmentioning

confidence: 93%

Zinc Antagonizes Homocysteine-Induced Fetal Heart Defects in Rats

Xiao

Zeng

et al. 2009

Cardiovasc Toxicol

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It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

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Section: Discussionmentioning

confidence: 93%

Zinc Antagonizes Homocysteine-Induced Fetal Heart Defects in Rats

Xiao

Zeng

et al. 2009

Cardiovasc Toxicol

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“…The association between MTRR A66G/ MTR A2756G and the risk of CHD has been reported among numerous studies [19], [20], [21], [22], [23], [24], [25], [26], [27]. However, despite these hard won successes begin to shed light on pathogenic mechanisms of CHD, such approaches have struggled to provide replicable results for the association.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variant in MTRR, but Not MTR, Is Associated with Risk of Congenital Heart Disease: An Integrated Meta-Analysis

et al. 2014

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BackgroundCongenital heart disease (CHD) is one of the most common birth defects and the leading cause of deaths among individuals with congenital structural abnormalities worldwide. Both Methionine synthase reductase (MTRR) and Methionine synthase (MTR) are key enzymes involved in the metabolic pathway of homocysteine, which are significant in the earlier period embryogenesis, particularly in the cardiac development. Evidence is mounting for the association between MTRR A66G (rs1801394)/MTR A2756G (rs1805087) and the CHD risk, but results are controversial. Therefore, we conducted a meta-analysis integrating case-control and transmitted disequilibrium test (TDT) studies to obtain more precise estimate of the associations of these two variants with the CHD risk.MethodsTo combine case-control and TDT studies, we used the Catmap package of R software to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 9 reports were included in the final meta-analysis. Eight of them comprised of 914 cases, 964 controls, and 441 families that were germane to MTRR A66G polymorphism; and 4 reports comprised of 250 cases, 205 controls, and 53 families that were relevant to MTR A2756G polymorphism. The pooled OR for the MTRR 66 G allele versus A allele was 1.35 (95% CI = 1.14–1.59, P<0.001, P heterogeneity = 0.073). For MTR A2756G, the G allele conferred a pooled OR of 1.10 (95% CI = 0.78–1.57, P = 0.597, P heterogeneity = 0.173) compared with the A allele. Sensitivity analyses were carried out to asses the effects of each individual study on the pooled OR, indicating the stability of the outcome. Moreover, positive results were also obtained in all subgroups stratified by study type and ethnicity except the subgroup of TDT studies in MTRR A66G variant.ConclusionsThis meta-analysis demonstrated a suggestive result that the A66G variant in MTRR, but not the A2756G in MTR, may be associated with the increase of CHD risks.

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“…The association between the MTHFR A1298C variant and CHD has been assessed in two case-control studies [9,27] where no association between the MTHFR A1298C variant and CHD was found. Similarly, no evidence of an [20].…”

Section: Discussionmentioning

confidence: 99%

The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population

et al. 2015

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Conotruncal heart defects (CTHDS) are a subgroup of congenital heart malformations that are considered to be a folate-sensitive birth defect. It has been hypothesized that polymorphisms in genes that code for key enzymes in the folate pathway may alter enzyme activity, leading to disruptions in folate metabolism and thus may influence the risk of such heart defects. This study was designed to investigate the association of six selected folate-metabolizing gene polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This was a case-control study involving 96 cases of CTHDs and 100 control samples, ranging in age from birth to 18 years. Genotyping using Sanger sequencing was performed for six single nucleotide polymorphisms of genes involved in folate metabolism. Logistic regression analyses revealed that for the 5,10-methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote genotype was associated with a significantly increased risk of CTHDs. The results of this study support an association between the inherited MTHFR A1298C genotype and the risk of CTHDs in an Indian population.

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Homocysteine Concentrations and Molecular Analysis in Patients with Congenital Heart Defects

Cited by 32 publications

References 35 publications

Zinc Antagonizes Homocysteine-Induced Fetal Heart Defects in Rats

Zinc Antagonizes Homocysteine-Induced Fetal Heart Defects in Rats

Genetic Variant in MTRR, but Not MTR, Is Associated with Risk of Congenital Heart Disease: An Integrated Meta-Analysis

The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population

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