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Homocysteine and gene hypomethylation

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https://www.readbyqxmd.com/read/27659321/maternal-mthfr-polymorphism-677-c-t-and-risk-of-down-s-syndrome-child-meta-analysis
#1
Amandeep Kaur, Anupam Kaur
Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down's syndrome (DS) child. A total of 37 case-control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers...
September 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27509954/methyl-donor-status-influences-dnmt-expression-and-global-dna-methylation-in-cervical-cancer-cells
#2
Natwadee Poomipark, Janet E Flatley, Marilyn H Hill, Barbara Mangnall, Elnaz Azar, Peter Grabowski, Hilary J Powers
BACKGROUND: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyldonor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. MATERIALS AND METHODS: The human cervical cancer cell line, C4 II, was grown in complete medium and medium depleted of folate (FM+) and folate and methionine (FM)...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27221153/fabp4-mediated-homocysteine-induced-cholesterol-accumulation-in-thp-1-monocyte-derived-macrophages-and-the-potential-epigenetic-mechanism
#3
Yideng Jiang, Shengchao Ma, Huiping Zhang, Xiaoling Yang, Guan Jun Lu, Hui Zhang, Yangyang He, Fanqi Kong, Anning Yang, Hua Xu, Minghao Zhang, Yun Jiao, Guizhong Li, Jun Cao, Yuexia Jia, Shaoju Jin, Jun Wei, Yingkang Shi
Hyperhomocysteinemia (HHcy) is an independent risk factor for the development of atherosclerosis (AS), according to overwhelming number of clinical and epidemiological studies. However, the underlying pathogenic molecular mechanisms by which HHcy promotes AS remain to be fully elucidated. Fatty acid binding protein 4 (FABP4) has been shown to be important in macrophage cholesterol trafficking. The objective of the present study was to determine whether homocysteine (Hcy) accelerates AS through regulating FABP4, and then mediates cholesterol accumulation in macrophages...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27175774/ratio-of-s-adenosylmethionine-to-s-adenosylhomocysteine-as-a-sensitive-indicator-of-atherosclerosis
#4
Huiping Zhang, Zhihong Liu, Shengchao Ma, Hui Zhang, Fanqi Kong, Yangyang He, Xiaoling Yang, Yanhua Wang, Hua Xu, Anning Yang, Jue Tian, Minghao Zhang, Jun Cao, Yideng Jiang, Xiong Guo
The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE)-/- mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high‑performance liquid chromatography...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26595280/methionine-synthase-a2756g-variation-is-associated-with-the-risk-of-retinoblastoma-in-iranian-children
#5
Mohammad Taghi Akbari, Asieh Naderi, Leila Saremi, Arezou Sayad, Shiva Irani, Ali Ahani
Association of epigenetic modifications with cancer has been widely studied. Gene-specific hypermethylation and global DNA hypomethylation are the most frequently observed patterns in great number of tumors. The methionine synthase (MTR) gene plays key role in maintaining adequate intracellular folate, methionine and normal homocysteine concentrations and, its polymorphism have been associated with the risk of retinoblastoma and other neoplasms. We evaluated the association of MTR A2756G polymorphism with the risk of retinoblastoma in an Iranian population...
December 2015: Cancer Epidemiology
https://www.readbyqxmd.com/read/26497014/effect-of-the-one%C3%A2-carbon-unit-cycle-on-overall-dna-methylation-in-children-with-down-s-syndrome
#6
Cui Song, Jingyi He, Jie Chen, Youxue Liu, Feng Xiong, Yutian Wang, Tingyu Li
DNA methylation is a major epigenetic mechanism regulating gene expression. In order to analyze the impact of the one‑carbon unit cycle on the overall level of DNA methylation in children with Down's syndrome (DS), the levels of indicators associated with the one‑carbon unit cycle, including folic acid (FA), vitamin B12 (VB12) and homocysteine (Hcy), and the overall DNA methylation level of DS and healthy controls (HCs) were determined in the present study. A total of 36 DS children and 40 age‑ and gender‑matched HCs were included in the present study to determine the levels of FA, VB12, Hcy and overall DNA methylation...
December 2015: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26170200/metabolomic-analysis-revealed-the-role-of-dna-methylation-in-the-balance-of-arachidonic-acid-metabolism-and-endothelial-activation
#7
Shan-Shan Xue, Jin-Long He, Xu Zhang, Ya-Jin Liu, Feng-Xia Xue, Chun-Jiong Wang, Ding Ai, Yi Zhu
Arachidonic acid (AA) metabolism plays an important role in vascular homeostasis. We reported that DNA hypomethylation of EPHX2 induced a pro-inflammatory response in vascular endothelial cells (ECs). However, the change in the whole AA metabolism by DNA methylation is still unknown. Using a metabolomic approach, we investigated the effect of DNA methylation on the balance of AA metabolism and the underlying mechanism. ECs were treated with a DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA), and AA metabolic profiles were analyzed...
October 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25822193/genomic-dna-hypomethylation-is-associated-with-neural-tube-defects-induced-by-methotrexate-inhibition-of-folate-metabolism
#8
Xiuwei Wang, Zhen Guan, Yan Chen, Yanting Dong, Yuhu Niu, Jianhua Wang, Ting Zhang, Bo Niu
DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs). However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS), liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS), microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR...
2015: PloS One
https://www.readbyqxmd.com/read/25763114/vitamin-b12-insufficiency-induces-cholesterol-biosynthesis-by-limiting-s-adenosylmethionine-and-modulating-the-methylation-of-srebf1-and-ldlr-genes
#9
Antonysunil Adaikalakoteswari, Sarah Finer, Philip D Voyias, Ciara M McCarthy, Manu Vatish, Jonathan Moore, Melissa Smart-Halajko, Nahla Bawazeer, Nasser M Al-Daghri, Philip G McTernan, Sudhesh Kumar, Graham A Hitman, Ponnusamy Saravanan, Gyanendra Tripathi
BACKGROUND: The dietary supply of methyl donors such as folate, vitamin B12, betaine, methionine, and choline is essential for normal growth, development, and physiological functions through the life course. Both human and animal studies have shown that vitamin B12 deficiency is associated with altered lipid profile and play an important role in the prediction of metabolic risk, however, as of yet, no direct mechanism has been investigated to confirm this. RESULTS: Three independent clinical studies of women (i) non-pregnant at child-bearing age, (ii) in early pregnancy, and (iii) at delivery showed that low vitamin B12 status was associated with higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL ratio...
2015: Clinical Epigenetics
https://www.readbyqxmd.com/read/25359865/homocysteine-accelerates-senescence-of-endothelial-cells-via-dna-hypomethylation-of-human-telomerase-reverse-transcriptase
#10
Donghong Zhang, Xiaoli Sun, Jianlan Liu, Xina Xie, Wei Cui, Yi Zhu
OBJECTIVE: Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity. APPROACH AND RESULTS: When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages...
January 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/25202269/altered-protein-phosphatase-2a-methylation-and-tau-phosphorylation-in-the-young-and-aged-brain-of-methylenetetrahydrofolate-reductase-mthfr-deficient-mice
#11
Jean-Marie Sontag, Brandi Wasek, Goce Taleski, Josephine Smith, Erland Arning, Estelle Sontag, Teodoro Bottiglieri
Common functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate and homocysteine metabolism, influence risk for a variety of complex disorders, including developmental, vascular, and neurological diseases. MTHFR deficiency is associated with elevation of homocysteine levels and alterations in the methylation cycle. Here, using young and aged Mthfr knockout mouse models, we show that mild MTHFR deficiency can lead to brain-region specific impairment of the methylation of Ser/Thr protein phosphatase 2A (PP2A)...
2014: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/24882549/dna-methylation-of-human-telomerase-reverse-transcriptase-associated-with-leukocyte-telomere-length-shortening-in-hyperhomocysteinemia-type-hypertension-in-humans-and-in-a-rat-model
#12
RANDOMIZED CONTROLLED TRIAL
Dong-hong Zhang, Xue-mei Wen, Lin Zhang, Wei Cui
BACKGROUND: Elevated homocysteine (Hcy) levels might play a role in the development of essential hypertension (EH). Telomere dynamics provide valuable insight into the pathogenesis of age-related diseases. The contribution of Hcy to leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was examined. METHODS AND RESULTS: LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene, T/S ratio) was inversely associated with age in patients with EH (n=258) and healthy controls (n=137), but significantly decreased with the Hcy level only in patients with hypertension after adjustment for age and sex...
2014: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/24841643/aberrant-dna-methylation-of-the-pdgf-gene-in-homocysteine%C3%A2-mediated-vsmc-proliferation-and-its-underlying-mechanism
#13
Xue-Bo Han, Hui-Ping Zhang, Cheng-Jian Cao, Yan-Hua Wang, Jue Tian, Xiao-Ling Yang, An-Ning Yang, Jie Wang, Yi-Deng Jiang, Hua Xu
It is well established that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS), which is characterized by vascular smooth muscle cell (VSMC) proliferation. However, the molecular mechanism underlying AS in VSMCs is yet to be elucidated. The aim of this study was to investigate the potential involvement of aberrant DNA methylation of the platelet‑derived growth factor (PDGF) gene in Hcy‑mediated VSMC proliferation and its underlying mechanism. Cultured human VSMCs were treated with varying concentrations of Hcy...
August 2014: Molecular Medicine Reports
https://www.readbyqxmd.com/read/24800750/mouse-model-for-deficiency-of-methionine-synthase-reductase-exhibits-short-term-memory-impairment-and-disturbances-in-brain-choline-metabolism
#14
Nafisa M Jadavji, Renata H Bahous, Liyuan Deng, Olga Malysheva, Marilyn Grand'maison, Barry J Bedell, Marie A Caudill, Rima Rozen
Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency...
July 15, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/24481135/sugar-and-auxin-signaling-pathways-respond-to-high-temperature-stress-during-anther-development-as-revealed-by-transcript-profiling-analysis-in-cotton
#15
Ling Min, Yaoyao Li, Qin Hu, Longfu Zhu, Wenhui Gao, Yuanlong Wu, Yuanhao Ding, Shiming Liu, Xiyan Yang, Xianlong Zhang
Male reproduction in flowering plants is highly sensitive to high temperature (HT). To investigate molecular mechanisms of the response of cotton (Gossypium hirsutum) anthers to HT, a relatively complete comparative transcriptome analysis was performed during anther development of cotton lines 84021 and H05 under normal temperature and HT conditions. In total, 4,599 differentially expressed genes were screened; the differentially expressed genes were mainly related to epigenetic modifications, carbohydrate metabolism, and plant hormone signaling...
March 2014: Plant Physiology
https://www.readbyqxmd.com/read/24330152/hypomethylation-of-long-interspersed-nucleotide-element-1-in-peripheral-mononuclear-cells-of-juvenile-systemic-lupus-erythematosus-patients-in-china
#16
Xiaolan Huang, Gaixiu Su, Zhen Wang, Shaofang Shangguan, Xiaodai Cui, Jia Zhu, Min Kang, Shengnan Li, Ting Zhang, Fengqi Wu, Li Wang
AIM: Methylation abnormalities in T lymphocytes have been reported to correlate with systemic lupus erythematosus (SLE). Previous studies identified hypomethylation in the promoter of several genes linked to SLE. Long interspersed nucleotide element-1 (LINE-1) constitutes 17-25% of the human genome, and LINE-1 hypomethylation has been reported in SLE. Limited information is available regarding LINE-1 methylation in juvenile SLE (JSLE). METHOD: Methylation levels of LINE-1 in peripheral blood mononuclear cells (PBMCs) from 59 JSLE and 47 control samples were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry...
March 2014: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/24040787/do-folate-vitamins-b%C3%A2-and-b%C3%A2-%C3%A2-play-a-role-in-the-pathogenesis-of-migraine-the-role-of-pharmacoepigenomics
#17
REVIEW
Munvar Miya Shaik, Huay Lin Tan, Mohammad A Kamal, Siew Hua Gan
Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate...
2014: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/24022817/the-metabolic-burden-of-methyl-donor-deficiency-with-focus-on-the-betaine-homocysteine-methyltransferase-pathway
#18
REVIEW
Rima Obeid
Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver...
September 9, 2013: Nutrients
https://www.readbyqxmd.com/read/23724740/folate-and-b12-in-prostate-cancer
#19
REVIEW
Simon M Collin
Mechanisms postulated to link folate and B12 metabolism with cancer, including genome-wide hypomethylation, gene-specific promoter hypermethylation, and DNA uracil misincorporation, have been observed in prostate tumor cells. However, epidemiological studies of prostate cancer risk, based on dietary intakes and blood levels of folate and vitamin B12 and on folate-pathway gene variants, have generated contradictory findings. In a meta-analysis, circulating concentrations of B12 (seven studies, OR = 1.10; 95% CI 1...
2013: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/23619570/hyperhomocysteinemia-induces-cardiac-injury-by-up-regulation-of-p53-dependent-noxa-and-bax-expression-through-the-p53-dna-methylation-in-apoe-mice
#20
Shengchao Ma, Huiping Zhang, Weiwei Sun, Huihui Gong, Yanhua Wang, Changjian Ma, Ju Wang, Chengjian Cao, Xiaoling Yang, Jue Tian, Yideng Jiang
Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease and has a strong correlation with heart failure. However, the effects of HHcy on cardiac tissue remain less well understood. To elucidate the role of p53-dependent apoptosis in HHcy-induced cardiac injury, we fed ApoE(-/-) mice with high methionine diet to establish HHcy model. Serum Hcy, cardiac enzymes, and lipids were measured. The protein levels of Noxa, DNMT1, caspases-3/9, and p53 were determined by enzyme-linked immunosorbent assay...
May 2013: Acta Biochimica et Biophysica Sinica
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