Association Between MTHFR C677T Polymorphism and Congenital Heart Disease

Liu, Peng Fei; Ding, Bing; Zhang, Jun‐Yi; Mei, Xiaofei; Li, Fēi; Wu, Peng; Mei, Chunhao; Zhou, Yafeng; Tan, Chongqing

doi:10.1536/ihj.19-389

Cited by 13 publications

(7 citation statements)

References 27 publications

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“…From the subgroup analysis, the increased risk of the T-allele was widely detected in Asians but not in Caucasians. Our results are compatible with the previous Meta analyses that investigated the association of the MTHFR C677T polymorphism in CHD [ 34 , 43 ]. Further, this association revealed through conventional meta-analysis has also been confirmed by performing Trial Sequential Analysis.…”

Section: Discussionsupporting

confidence: 93%

“Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case–control study encompassing meta-analysis and trial sequential analysis”

et al. 2022

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Background The risk of Congenital Heart Defects (CHD) is greatly influenced by variants within the genes involved in folate-homocysteine metabolism. Polymorphism in MTHFR (C677T and G1793A) and MS/MTR (A2756G) genes increases the risk of developing CHD risk, but results are controversial. Therefore, we conducted a case–control association pilot study followed by an up-dated meta-analysis with trial sequential analysis (TSA) to obtain more precise estimate of the associations of these two gene variants with the CHD risk. Methods For case–control study, we enrolled 50 CHD patients and 100 unrelated healthy controls. Genotyping was done by PCR–RFLP method and meta-analysis was performed by MetaGenyo online Statistical Analysis System software. For meta-analysis total number of individuals was as follows: for MTHFR C677T 3450 CHD patients and 4447 controls whereas for MS A2756G 697 CHD patients and 777 controls. Results Results of the original pilot study suggested lack of association for MTHFR C677T and MS A2756G polymorphism with risk of CHD whereas MTHFR G1793A was significantly associated with the disease. On performing meta-analysis, a significant association was observed with MTHFR C677T polymorphism but not with MS A2756G. Trial sequential Analysis also confirmed the sufficient sample size requirement for findings of meta-analysis. Conclusions The results of the meta-analysis suggested a significant role of MTHFR in increased risk of CHD.

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Section: Discussionsupporting

confidence: 93%

“Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case–control study encompassing meta-analysis and trial sequential analysis”

et al. 2022

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“…Recently, mutations associated with MTHFR have been identified and linked with the susceptibility to developing an array of health complications. Indeed, mutations such as the MTHFR gene C677T have been closely associated with congenital heart disease and other cardiovascular disease risk factors, including hyperhomocysteinemia, hyperlipidemia and blood pressure [ 30 , 31 , 32 , 33 ]. Interestingly, NAFLD patients were previously shown to present with increased plasma homocysteine (Hcy), along with MTHFR C677T, when compared with healthy controls, further highlighting the involvement of MTHFR in the disease onset and progression [ 31 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice

Mabasa

Kotze

Shabalala

et al. 2022

IJERPH

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of hepatic metabolic perturbations ranging from simple steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. Currently, lifestyle modifications to reduce weight gain are considered the most effective means of preventing and treating the disease. The aim of the present study was to determine the therapeutic benefit of Sclerocarya birrea (Marula leaf extract, MLE) on hepatic steatosis. Obese db/db mice were randomly stratified into the obese control, metformin (MET) or MLE-treated groups. Mice were treated daily for 29 days, at which point all mice were euthanized and liver samples were collected. Hematoxylin and eosin staining was used for histological assessment of the liver sections, while qRT-PCR and Western blot were used to determine hepatic mRNA and protein expression, respectively. Thereafter, the association between methylenetetrahydrofolate reductase (Mthfr a key enzyme in one-carbon metabolism and DNA-methylation-induced regulation of gene transcription) and lipogenic genes was evaluated using Pearson’s correlation coefficient. Mice treated with MLE presented with significantly lower body and liver weights as compared with the obese control and MET-treated mice (p ≤ 0.05). Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control and MET-treated mice (p ≤ 0.05). The reduced lipid accumulation was associated with low expression of fatty acid synthase (Cpt1; p ≤ 0.05) and an upregulation of the fatty acid oxidation gene, carnitine palmitoyltransferase (Cpt1; p ≤ 0.01), as compared with the obese control mice. Interestingly, MLE treatment improved the correlation between Mthfr and Cpt1 mRNA expression (r = 0.72, p ≤ 0.01). Taken together, the results suggest that Marula leaf extracts may inhibit hepatic steatosis by influencing the association between Mthfr and genes involved in hepatic lipid metabolism. Further studies are warranted to assess DNA methylation changes in lipid metabolism genes.

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“…The rs1801133 MTHFR polymorphism affected the optimal activity of the enzyme (11) and increased the level of homocysteine (8) and the other variation (MTHFR A1298C) within the presumed regulatory domine also inhibited the enzyme activity (12). It is worth noting that findings from previous studies involved in the association of the two genetic mutations with the risk of CHD were conflicting (13,14). Additionally, previous studies focused mainly on the abovementioned loci and have ignored the other MTHFR gene loci.…”

Section: Introductionmentioning

confidence: 99%

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease

et al. 2022

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BackgroundTo systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.MethodsA case–control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association.ResultsOur findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34–2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22–2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52–23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99–13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58–3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36–2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68–7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed.ConclusionAn association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations.Registration numberhttp://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

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Association Between MTHFR C677T Polymorphism and Congenital Heart Disease

Cited by 13 publications

References 27 publications

“Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case–control study encompassing meta-analysis and trial sequential analysis”

“Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case–control study encompassing meta-analysis and trial sequential analysis”

Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease

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