DNA methylation status of the methylenetetrahydrofolate reductase gene promoter in peripheral blood of end-stage renal disease patients
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End-stage renal disease (ESRD) is one of the main causes of morbidity and mortality worldwide. DNA methylation is a major epigenetic modification of the genome that has the potential to silence gene expression. Methylenetetrahydrofolate reductase (MTHFR) gene inactivation was recognized as a predisposing factor of hyperhomocysteinemia in renal patients. The current study aimed to determine the methylation status within the MTHFR promoter region in DNA isolated from peripheral blood of ESRD patients and controls and the correlation of this methylation with the clinical and biochemical characteristics in ESRD patients. Ninety-six ESRD patients and 96 healthy ethnically, age and gender matched controls were included within the study. MTHFR promoter methylation was assessed using methylation specific polymerase chain reaction. The frequency of MTHFR methylation was significantly higher in ESRD patients than in controls (P = 0.003), additionally, MTHFR methylation was associated to a decrease in estimated glomerular filtration rate, serum high-density lipoprotein cholesterol level and an increase in both serum total cholesterol and low-density lipoprotein cholesterol levels. Data generated from this study suggest the possible involvement of MTHFR promoter methylation in the pathogenesis of ESRD and support a new dimension of MTHFR inactivation.
KeywordsEnd-stage renal disease Methylenetetrahydrofolate reductase DNA methylation Epigenetics
- 12.Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, Heimburger O, Barany P, Alvestrand A, Nordfors L, Qureshi AR, Ekstrom TJ, Schalling M (2007) Impact of inflammation on epigenetic DNA methylation—a novel risk factor for cardiovascular disease? J Intern Med 261(5):488–499. doi: 10.1111/j.1365-2796.2007.01777.x CrossRefPubMedGoogle Scholar
- 19.Wu W, Shen O, Qin Y, Niu X, Lu C, Xia Y, Song L, Wang S, Wang X (2010) Idiopathic male infertility is strongly associated with aberrant promoter methylation of methylenetetrahydrofolate reductase (MTHFR). PLoS One 5(11):e13884. doi: 10.1371/journal.pone.0013884 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Winkelmayer WC, Kramar R, Curhan GC, Chandraker A, Endler G, Fodinger M, Horl WH, Sunder-Plassmann G (2005) Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: a prospective study. J Am Soc Nephrol 16(1):255–260. doi: 10.1681/asn.2004070576 CrossRefPubMedGoogle Scholar
- 31.Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz J, Yang F, Durante W, Chan L, Schafer AI, Pownall HJ, Yang X, Wang H (2006) Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I protein synthesis and enhancing HDL cholesterol clearance. Circ Res 99(6):598–606. doi: 10.1161/01.res.0000242559.42077.22 CrossRefPubMedPubMedCentralGoogle Scholar