<i>MTHFR</i>
            Gene and Serum Folate Interaction on Serum Homocysteine Lowering

Huang, Xiao; Qin, Xianhui; Yang, Wen‐Bin; Liu, Lishun; Jiang, Chongfei; Zhang, Xianglin; Jiang, Shanqun; Bao, Huihui; Su, Hai; Ping, Li; He, Minqiang; Song, Yun; Zhao, Min; Yin, Dou; Wang, Yu; Zhang, Yan; Li, Jianping; Yang, Runhuai; Wu, Yanqing; Hong, Kui; Wu, Qinhua; Chen, Yundai; Sun, Ning; Li, Xiaoying; Tang, Genfu; Zhang, Yuanyuan; Cai, Yefeng; Hou, Fan Fan; Huo, Yong; Wang, Hong; Wang, Xiaobin; Cheng, Xiaoshu

doi:10.1161/atvbaha.117.310211

Cited by 35 publications

(37 citation statements)

References 44 publications

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“…Therefore, in our study, we selected two GRS methods, SC-GRS and wGRS (DL-GRS), to analyse the efficacy on efficacy of folic acid treatment for HHcy. The direction of the six SNP affecting the efficacy of folic acid therapy was consistent with previous studies (17,18,(24)(25)(26)(27) . Especially, three SNP (rs1801131, rs1801133 and rs1801394) showed significant association with the folic acid efficacy.…”

Section: Discussionsupporting

confidence: 90%

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Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Zhang

Liu

et al. 2019

Br J Nutr

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No risk assessment tools for the efficacy of folic acid treatment for hyperhomocysteinaemia (HHcy) have been developed. We aimed to use two common genetic risk score (GRS) methods to construct prediction models for the efficacy of folic acid therapy on HHcy, and the best gene–environment prediction model was screened out. A prospective cohort study enrolling 638 HHcy patients was performed. We used a logistic regression model to estimate the associations of two GRS methods with the efficacy. Performances were compared using area under the receiver operating characteristic curve (AUC). The simple count genetic risk score (SC-GRS) and weighted genetic risk score (wGRS) were found to be independently associated with the efficacy of folic acid treatment for HHcy. Using the SC-GRS, per risk allele increased with a 1·46-fold increased failure risk (P < 0·001) after adjustment for traditional risk factors, including age, sex, BMI, smoking, alcohol consumption, history of diabetes, history of hypertension, history of hyperlipidaemia, history of stroke and history of CHD. When used the wGRS, the association was strengthened (OR = 2·08, P < 0·001). Addition of the SC-GRS and wGRS to the traditional risk model significantly improved the predictive ability by AUC (0·859). A precise gene–environment predictive model with good performance was developed for predicting the treatment failure rate of folic acid therapy for HHcy.

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Section: Discussionsupporting

confidence: 90%

“…We selected six previously identified SNP affecting the efficacy of folic acid therapy (17,18,(24)(25)(26)(27) . All these SNP had minor allele frequency > 0•05 in the Chinese population.…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Zhang

Liu

et al. 2019

Br J Nutr

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“…In those who are homozygous for the mutation (TT genotype), enzyme function is only 30% of normal, and data provide evidence that nutrition can counteract genetic susceptibility. Recently, large, randomized trial in a population without mandatory FA fortification demonstrated that the adverse effect of the TT genotype on tHcy levels can be ameliorated by raising serum folate levels above the threshold (15 ng/mg or 34 nmol/L) via FA treatment and it provides new evidence to support a personalized FA treatment [94]. The gene-nutrient interaction between MTHFR C677T variant and folate status was also observed on the risk of anencephaly.…”

Section: Epigenetic Genetic and Nutrigenomic Risk Factors For Congementioning

confidence: 97%

“…Low folate status (as defined by various measures including blood folate concentrations, folate intake, and/or FA intake) has been associated with an increased risk of cardiovascular disease, cancers, CAs, CHD, and NTD [5,6,[89][90][91][92][93][94]. Also, this deficiency is clearly detrimental to the embryo and shows possible longer-term risks of diabetes or other health outcomes and health problems associated with child mortality and morbidity [95].…”

Section: Epigenetic Genetic and Nutrigenomic Risk Factors For Congementioning

confidence: 99%

“…Previous tHcy-lowering trials have not considered whether and to what extent these factors could modify the efficacy of folic acid (FA) treatment. In some countries with folate fortification like America, Australia, and New Zealand, the effect of TT genotype is not so obvious like in Asia region where folate intake is low [94]. In those who are homozygous for the mutation (TT genotype), enzyme function is only 30% of normal, and data provide evidence that nutrition can counteract genetic susceptibility.…”

Section: Epigenetic Genetic and Nutrigenomic Risk Factors For Congementioning

confidence: 99%

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Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

Stanković¹

2020

DNA Methylation Mechanism

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During the last decade, quantitative measurement of the methylation status in white blood cells (WBCs) has been used as a potential biomarker in a variety of diseases. Long interspersed nucleotide element-1 (LINE-1) has been used widely as a surrogate marker of global DNA methylation. Altered maternal DNA methylation is suggested to be an underlying mechanism in the trisomy 21 and the development of birth defects, including congenital heart defects (CHDs). The molecular mechanisms that underlie the epigenetic regulation of gene transcription are independent of DNA sequence, but they do depend on environmental stimuli, which are especially important in fetal development in utero environment. Folic acid deficiency and genetic variations of folate pathway genes, such as the methylenetetrahydrofolate reductase gene (MTHFR), are foremost among these maternal risk factors. Also, there are exogenous risk factors (cigarette smoking, alcohol intake, medication use, periconceptional maternal supplementation, body mass index, and dietary habits) with impact on maternal LINE-1 methylation. MTHFR C677T genotype/ diet and other environmental factors as significant predictors of LINE-1 DNA methylation in regard to congenital diseases will be discussed in the chapter.

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