血红素加氧酶-1启动子区多态性与疾病易感性的关系

Association between heme oxygenase-1 gene promoter polymorphism and the susceptibility of human disease

血红加氧酶-1(HO-1)是一种诱导性抗氧化防御酶,可分解血红素释放出游离铁、一氧化碳和胆绿素,后者可迅速转化为胆红素,这三种代谢产物具有抗炎、抗氧化、抗增殖的作用。HO-1在大多数组织内呈低水平表达,可被多种伤害性刺激诱导产生高水平表达,从而在维持细胞内稳态方面起着重要作用。最近研究表明其基因启动子区5′端区域的2个突变可影响其转录水平,并且与多种疾病的发生发展密切相关,本文就此2个位点的多态性对HO-1的功能及其临床方面的意义作一综述。

Heme oxygenase-1 （ HO-1 ）, the inducible isoform of heine oxygenase, is a cytoprotective enzyme that plays a central role in the defense against oxidative. HO-1 catalyzes the degradation of heme into iron, carbon monoxide （CO）, and biliverdin, which is quickly converted into bilirubin. These downstream products of heme catabolism have recently been found to be some protective factors with potent anti-inflammatory, anti-oxidant, and anti-proliferative effects. Although HO-1 is expressed in various tissues at a low level, and is upregulated by multiple adverse stimuli, thus it plays an important role in keeping cell redox homeostasia under various pathophysiological conditions. From several studies it seems that two potentially function polymorphisms in the 5＇-flanking region of human HO-1 gene promoter modulate the quantitative level of HO-1 activity, and the polymorphisms were shown to be associated with susceptibility to various disease, so the present article focuses on the role of this two polymorphisms on its function as well as disease susceptibility.