在接受治疗的胱硫醚β-合酶（CBS）缺乏症患者中，DNA甲基化状态未受损害。

DNA methylation status is not impaired in treated cystathionine beta-synthase (CBS) deficient patients.

作者信息

Heil Sandra G, Riksen Niels P, Boers Godfried H, Smulders Yvo, Blom Henk J

机构信息

Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.

出版信息

Mol Genet Metab. 2007 May;91(1):55-60. doi: 10.1016/j.ymgme.2007.01.008. Epub 2007 Mar 2.

DOI:10.1016/j.ymgme.2007.01.008

PMID:17336565

Abstract

BACKGROUND

Cystathionine beta-synthase (CBS) deficiency is an inborn error of metabolism that is biochemically characterized by severe hyperhomocysteinemia and homocystinuria. In tissues of mice deficient for CBS it has been demonstrated that global DNA methylation and DNA methylation of the H19 differentially methylated region (DMR) were impaired. In this study we aimed to investigate whether DNA methylation is disturbed in patients with hyperhomocysteinemia due to CBS-deficiency.

METHODS

Genomic DNA was isolated from heparin blood from nine CBS deficient patients that were treated with homomcysteine-lowering therapy and eight healthy controls. Global DNA methylation was measured by liquid chromatography-electrospay ionization-tandem mass spectrometry and gene-specific DNA methylation of the H19 DMR was determined by bisulphite-sequencing.

RESULTS

Homocysteine, AdoMet and AdoHcy levels were significantly elevated, whereas no differences in AdoMet:AdoHcy ratio were observed in plasma of treated CBS deficient patients compared with controls. Global DNA methylation and gene-specific DNA methylation of the H19 DMR was not different between CBS deficient patients and controls.

CONCLUSION

We demonstrate that DNA methylation is not impaired in treated CBS deficient patients. Further studies are necessary to investigate the precise role of homocysteine-lowering therapy in relation to DNA methylation in patients with homocystinuria.

摘要

背景

胱硫醚β合酶（CBS）缺乏症是一种先天性代谢缺陷，其生化特征为严重的高同型半胱氨酸血症和同型胱氨酸尿症。在CBS缺乏的小鼠组织中已证明，整体DNA甲基化以及H19差异甲基化区域（DMR）的DNA甲基化均受到损害。在本研究中，我们旨在调查由于CBS缺乏导致的高同型半胱氨酸血症患者的DNA甲基化是否受到干扰。