Association of DNMT1 Gene Polymorphisms with Congenital Heart Disease in Child Patients

Wang, Feng‐Yu; Zhou, Shuyao; Wang, Yanli; Wang, Lina; Zhou, Jack G.; Wang, HaiLi; Li, Cong-min; Chang, Mingxiu

doi:10.1007/s00246-015-1093-9

Cited by 8 publications

(11 citation statements)

References 23 publications

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“…CHD may be caused by genetic or environmental factors, but is usually a combination of the two sides [ 2 – 7 ]. It has been recognized that multiple environmental factors can increase the CHD risk through their influences on gravida during pregnancy, such as viral infection, chemical, and maternal diseases [ 8 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Association Between DSCR1 Variations and Congenital Heart Disease Susceptibility

Guo

Bai

et al. 2015

Med Sci Monit

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BackgroundThe objective of this study was aimed to detect the association of Down syndrome critical region 1 (DSCR1) gene polymorphisms (rs149048873 and rs143081213) and congenital heart disease (CHD) susceptibility.Material/MethodsThis case-control study included 102 CHD patients and 113 healthy controls. Cases and controls were matched in age and gender. Genotypes of DSCR1 gene polymorphisms were detected by TaqMan method in cases and controls. Hardy-Weinberg equilibrium (HWE) examination was performed by PLINK 1.0 software. Chi square test was utilized to assess the distribution of the genotypes and the alleles. Relative risk of CHD was presented by odds ratios (ORs) with 95% confidence intervals (CIs). All of the calculations were implemented using SPSS 18.0.ResultsVariant genotype distribution of rs149048873 and rs143081213 mutations were higher in cases than in controls, but the differences were not statistically obvious (P>0.05). Additionally, frequencies of mutant allele of the two polymorphisms were also significantly different in case and control groups (P>0.05).ConclusionsNo significant associations existed between DSCR1 gene rs149048873 and rs143081213 polymorphisms and CHD susceptibility.

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Section: Introductionmentioning

confidence: 99%

Association Between DSCR1 Variations and Congenital Heart Disease Susceptibility

Guo

Bai

et al. 2015

Med Sci Monit

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“…In contrast to the de novo catalytic activity of DNMT3A and DNMT3B, DNMT1 is responsible for maintaining methylation patterns [ 19 ]. Several previous studies have shown that DNMT1 polymorphisms (rs16999593, rs2228612) are associated with the risk of developing CHDs [ 23 ], and that the decreased expression of DNMT1 may play an important role in the pathogenesis of tetralogy of Fallot [ 30 ]. Researchers have also suggested that DNMT1 rs16999593 reduces the risk of the transposition of the great arteries [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Genetic variation caused by SNPs is the most common form of change in the gene structure, and it may influence gene expression. Literature evidence suggests that polymorphisms of the MTHFR , MTRR, and DNMTs genes could be a risk factor for CHDs; however, the results are inconsistent [ 23 , 24 , 25 ]. Specifically, the MTHFR 677C>T (rs1801133) polymorphism is a common genetic variation that affects the function of the MTHFR enzyme.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that the MTRR 66A>G polymorphism leads to decreased MTRR enzyme activity and reduced efficiency in the remethylation of homocysteine to methionine [ 27 ]. The most studied DNMT1 SNPs are 97T>C (rs16999593), +32204A>G (rs2228611), and 327A>G (rs2228612), which exist in the coding regions and, consequently, may influence the DNMT1 expression [ 23 , 28 , 29 ]. Two common polymorphisms have been identified in the promoter region of the DNMT3B gene: −149C>T (rs2424913) and −579G>T (rs1569686).…”

Section: Introductionmentioning

confidence: 99%

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DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome

Majstorović

Barišić

Božović

et al. 2023

Genes

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Impairments of the genes that encode enzymes that are involved in one-carbon metabolism because of the presence of gene polymorphisms can affect the methylation pattern. The altered methylation profiles of the genes involved in cardiogenesis may result in congenital heart defects (CHDs). The aim of this study was to investigate the association between the MTHFR rs1801133, MTHFR rs1801131, MTRR rs1801394, DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms and congenital heart defects in Down syndrome (DS) individuals. The study was conducted on 350 participants, including 134 DS individuals with CHDs (DSCHD+), 124 DS individuals without CHDs (DSCHD−), and 92 individuals with non-syndromic CHD. The genotyping was performed using the PCR–RFLP method. A statistically significant higher frequency of the DNMT3B rs2424913 TT in the DSCHD+ individuals was observed. The DNMT3B rs2424913 TT genotype, as well as the T allele, had significantly higher frequencies in the individuals with DS and atrial septal defects (ASDs) in comparison with the individuals with DS and other CHDs. Furthermore, our results indicate a statistically significant effect of the DNMT3B rs1569686 TT genotype in individuals with non-syndromic CHDs. The results of the study suggest that the DNMT3B rs2424913 TT genotypes may be a possible predisposing factor for CHDs in DS individuals, and especially those with ASDs.

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“…There is reported reduction in DNMT1 following the loss of LSD1 in mouse embryonic stem cells (Nicholson et al, 2013). DNMT1 polymorphisms, namely rs16999593, rs2228612, and rs10420321 are implicated in the risk of CHD (Wang et al, 2015). Additionally, significant upregulation of DNMT1 and downregulation of DNMT3A and 3B have been reported in the vitamin A‐deficient embryos showing higher incidence of CHD indicating aberrant methylation as the key event contributing to the etiology of CHD in these circumstances (Hendrich, Guy, Ramsahoye, Wilson, & Bird, 2001).…”

Section: Introductionmentioning

confidence: 99%

The study of expression levels of DNA methylation regulators in patients affected with congenital heart defects (CHDs)

Joshi¹,

Kukshal²,

Chellappan³

et al. 2022

Birth Defects Research

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Background: Congenial heart defects (CHDs) have multifactorial etiology with complex interplay of genetic and environmental factors. Environmental impact can have epigenetic mechanism of CHD development. Many studies have reported the causal association between CHD and distinct DNA methylation profile which is one of the key epigenetic events, which has vital role in normal embryonic development. The products of DNMT1, DNMT3A, DNMT3B, and MBD2 are important regulators of DNA methylation process.Changes in the expression of these genes are implicated in congenital structural cardiac defects. Hence, in this proof-of-concept study, we have compared the expression levels of these genes in the blood samples of healthy controls and CHD cases while investigating the etiology of CHD. Methods: In this study with 48 CHD cases and 47 healthy controls, total RNA was isolated from the whole blood samples using TRI reagent. Quantitative RT PCR (qRT-PCR) was used to analyze the mRNA levels of DNMT1, DNMT3A, DNMT3B, and MBD2. The expression levels have been analyzed by relative quantification. Results: We observed that DNMT3B (fold change = À2.563; p = .0018) and DNMT3A (fold change = À2.169; p = .05) were significantly downregulated in CHD patients, whereas the expression of DNMT1 and MBD2 was not significantly different between cases and controls.Conclusions: Lower expression of de novo methyltransferases, namely, DNMT3B and DNMT3A in CHD cases, may be an important contributor to the mechanism of CHD pathogenesis. Further studies with age-matched controls and analysis of global DNA methylation profile are required to investigate the proposed causal association.

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Association of DNMT1 Gene Polymorphisms with Congenital Heart Disease in Child Patients

Cited by 8 publications

References 23 publications

Association Between DSCR1 Variations and Congenital Heart Disease Susceptibility

Association Between DSCR1 Variations and Congenital Heart Disease Susceptibility

DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome

The study of expression levels of DNA methylation regulators in patients affected with congenital heart defects (CHDs)

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