| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Molecular Diagnostics and Genetics |
1 Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, and
2 Centro de Nutrição e Metabolismo, Faculdade de Medicina da Universidade de Lisboa, 1649-039 Lisboa, Portugal.
3 Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
4 Department of Paediatrics, University Medical Center St. Radboud, 6500 HB Nijmegen, The Netherlands.
aAddress correspondence to this author at: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-039 Lisboa, Portugal. Fax 351-217946491; e-mail italmeida{at}ff.ul.pt.
Background: The pathogenic mechanism of homocysteine’s effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology.
Methods: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls.
Results: Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [3H]dCTP incorporation/µg of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios.
Conclusion: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  L. M. J. W. van Driel, M. J. C. Eijkemans, R. de Jonge, J. H. M. de Vries, J. B. J. van Meurs, E. A. P. Steegers, and R. P. M. Steegers-Theunissen Body Mass Index Is an Important Determinant of Methylation Biomarkers in Women of Reproductive Ages J. Nutr., December 1, 2009; 139(12): 2315 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Baccarelli, R. O. Wright, V. Bollati, L. Tarantini, A. A. Litonjua, H. H. Suh, A. Zanobetti, D. Sparrow, P. S. Vokonas, and J. Schwartz Rapid DNA Methylation Changes after Exposure to Traffic Particles Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 572 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mzhavia, S. Yu, S. Ikeda, T. T. Chu, I. Goldberg, and H. M. Dansky Neuronatin: A New Inflammation Gene Expressed on the Aortic Endothelium of Diabetic Mice Diabetes, October 1, 2008; 57(10): 2774 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Malanovic, I. Streith, H. Wolinski, G. Rechberger, S. D. Kohlwein, and O. Tehlivets S-Adenosyl-L-homocysteine Hydrolase, Key Enzyme of Methylation Metabolism, Regulates Phosphatidylcholine Synthesis and Triacylglycerol Homeostasis in Yeast: IMPLICATIONS FOR HOMOCYSTEINE AS A RISK FACTOR OF ATHEROSCLEROSIS J. Biol. Chem., August 29, 2008; 283(35): 23989 - 23999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. B. Nanayakkara, J. C. Kiefte-de Jong, C. D. A. Stehouwer, F. J. van Ittersum, M. R. Olthof, R. M. Kok, H. J. Blom, C. van Guldener, P. M. ter Wee, and Y. M. Smulders Association between global leukocyte DNA methylation, renal function, carotid intima-media thickness and plasma homocysteine in patients with stage 2-4 chronic kidney disease Nephrol. Dial. Transplant., August 1, 2008; 23(8): 2586 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Stenvinkel and T. J. Ekstrom Epigenetics--a helpful tool to better understand processes in clinical nephrology? Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1493 - 1496. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stenvinkel, J. J. Carrero, J. Axelsson, B. Lindholm, O. Heimburger, and Z. Massy Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient: How Do New Pieces Fit into the Uremic Puzzle? Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 505 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, Q. Wang, H. Guo, M. Xia, Q. Yuan, Y. Hu, H. Zhu, M. Hou, J. Ma, Z. Tang, et al. Plasma S-Adenosylhomocysteine Is a Better Biomarker of Atherosclerosis Than Homocysteine in Apolipoprotein E-Deficient Mice Fed High Dietary Methionine J. Nutr., February 1, 2008; 138(2): 311 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Devlin, R. Singh, R. E. Wade, S. M. Innis, T. Bottiglieri, and S. R. Lentz Hypermethylation of Fads2 and Altered Hepatic Fatty Acid and Phospholipid Metabolism in Mice with Hyperhomocysteinemia J. Biol. Chem., December 21, 2007; 282(51): 37082 - 37090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wagner and M. J Koury S-Adenosylhomocysteine a better indicator of vascular disease than homocysteine? Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1581 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P Stabler, R. H Allen, E. T Dolce, and M. A. Johnson Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1422 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gellekink, D. van Oppenraaij-Emmerzaal, A. van Rooij, E. A. Struys, M. den Heijer, and H. J. Blom Stable-Isotope Dilution Liquid Chromatography-Electrospray Injection Tandem Mass Spectrometry Method for Fast, Selective Measurement of S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma Clin. Chem., August 1, 2005; 51(8): 1487 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Devlin, T. Bottiglieri, F. E. Domann, and S. R. Lentz Tissue-specific Changes in H19 Methylation and Expression in Mice with Hyperhomocysteinemia J. Biol. Chem., July 8, 2005; 280(27): 25506 - 25511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, L. Pickell, Y. Liu, Q. Wu, J. S Cohn, and R. Rozen Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate lead to adverse reproductive outcomes and congenital heart defects in mice Am. J. Clinical Nutrition, July 1, 2005; 82(1): 188 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-L Gueant, G Anello, P Bosco, R-M Gueant-Rodriguez, A Romano, C Barone, P Gerard, and C Romano Homocysteine and related genetic polymorphisms in Down's syndrome IQ J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 706 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Ulrey, L. Liu, L. G. Andrews, and T. O. Tollefsbol The impact of metabolism on DNA methylation Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R139 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zaina, M. W. Lindholm, and G. Lund Nutrition and Aberrant DNA Methylation Patterns in Atherosclerosis: More than Just Hyperhomocysteinemia? J. Nutr., January 1, 2005; 135(1): 5 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M Guerra-Shinohara, O. E Morita, S. Peres, R. A Pagliusi, L. F Sampaio Neto, V. D'Almeida, S. P Irazusta, R. H Allen, and S. P Stabler Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1312 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Ames Supplements and Tuning Up Metabolism J. Nutr., November 1, 2004; 134(11): 3164S - 3168S. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Narayanan, J. McConnell, J. Little, L. Sharp, C. J. Piyathilake, H. Powers, G. Basten, and S. J. Duthie Associations between Two Common Variants C677T and A1298C in the Methylenetetrahydrofolate Reductase Gene and Measures of Folate Metabolism and DNA Stability (Strand Breaks, Misincorporated Uracil, and DNA Methylation Status) in Human Lymphocytes In vivo Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1436 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lund, L. Andersson, M. Lauria, M. Lindholm, M. F. Fraga, A. Villar-Garea, E. Ballestar, M. Esteller, and S. Zaina DNA Methylation Polymorphisms Precede Any Histological Sign of Atherosclerosis in Mice Lacking Apolipoprotein E J. Biol. Chem., July 9, 2004; 279(28): 29147 - 29154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Castro, I Rivera, P Ravasco, M E Camilo, C Jakobs, H J Blom, and I T de Almeida 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->T and 1298A->C mutations are associated with DNA hypomethylation J. Med. Genet., June 1, 2004; 41(6): 454 - 458. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mizunuma, K. Miyamura, D. Hirata, H. Yokoyama, and T. Miyakawa Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae PNAS, April 20, 2004; 101(16): 6086 - 6091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Stabler and R. H. Allen Quantification of Serum and Urinary S-Adenosylmethionine and S-Adenosylhomocysteine by Stable-Isotope-Dilution Liquid Chromatography-Mass Spectrometry Clin. Chem., February 1, 2004; 50(2): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
