Relationship between microsatellite polymorphism in the haem oxygenase-1 gene promoter and longevity of the normal Japanese population
Relationship between microsatellite polymorphism in the haem oxygenase-1 gene promoter and longevity of the normal Japanese population
复制标题
血红素加氧酶1基因启动子微卫星多态性与日本正常人群寿命的关系
作者：
M. Yamaya;K. Nakayama;S. Ebihara;H. Hirai;S. Higuchi;H. Sasaki
氧化应激与癌症、肺部疾病、心脑血管疾病等多种疾病的发病有关。1-3 除了环境因素外，遗传因素也可能参与决定一个人对氧化应激诱发疾病的易感性。虽然这些基因型在老年人中更常见的情况并不明显，但由于大多数老年人都患有与年龄相关的疾病，具有一定保护性遗传背景的健康老年人可能会避免与年龄相关的疾病，并可能活到高龄。
血红素加氧酶 (HO) 将血红素氧化降解为胆绿素，随后胆绿素还原酶将其还原为胆红素（一种有效的活性氧清除剂）。 4 因为不仅 HO-1（一种 H2O 的诱导型形式），而且 H2O 的组成型形式（包括 HO-2）都可以提供细胞保护，防止血红素和非血红素介导的氧化损伤，4 H2O 被认为在抵御各种活性氧物质方面发挥着重要作用。
大鼠催乳素基因的 (GT)n 重复序列是多态性的，这种嘌呤-嘧啶交替序列具有 Z 构象潜力，会对大鼠催乳素基因的转录活性产生负面影响。5 人 HO-1 基因的 (GT)n 重复序列也是多态性的，6 并调节人 HO-1 基因转录。7 我们已经证明 HO-1 基因 (X14782) 中 (GT)n 重复序列的大尺寸（33≤ 重复序列）与日本人群对慢性肺气肿的易感性有关，并且被归类为 L 类等位基因的大 (GT)n 重复序列会抑制培养细胞系中过氧化氢诱导的 HO-1 基因转录。 8 基于这些发现，我们假设 HO-1 基因中 (GT)n 重复序列的数量与氧化应激诱发的疾病发展的易感性相关。
为了检验这个假设，我们筛选了……
Oxidative stress is associated with the pathogenesis of various diseases such as cancer, pulmonary disease, and cardiovascular and cerebrovascular disease.1–3 In addition to environmental factors, genetic factors may be involved in determining a person’s susceptibility to diseases induced by oxidative stress. Although it is not obvious that these genotypes might be more frequent in older people, as the majority of the elderly are subject to age related disorders, healthy elderly people with some protective genetic background may escape from age related disorders and can reach an advanced age.
Haem oxygenase (HO) oxidatively degrades haem to biliverdin, which is subsequently reduced to bilirubin, an efficient scavenger of reactive oxygen species, by biliverdin reductase.4 Because not only HO-1, an inducible form of HO, but also a constitutive form of HO, including HO-2, provide cellular protection against haem and non-haem mediated oxidant injury,4 HO is suggested to have an important role in protection against various reactive oxygen species.
A (GT)n repeat of the rat prolactin gene is polymorphic, and this purine-pyrimidine alternating sequence, with Z conformation potential, negatively affects transcriptional activity in the rat prolactin gene.5 A (GT)n repeat of the human HO-1 gene is also polymorphic,6 and modulates human HO-1 gene transcription.7 We have shown that the large size (33≤ repeat) of a (GT)n repeat in the HO-1 gene (X14782) is associated with susceptibility to chronic pulmonary emphysema in Japanese populations and that a large (GT)n repeat categorised as a class L allele inhibits HO-1 gene transcription induced by hydrogen peroxide in cultured cell lines.8 Based on these findings, we hypothesised that the number of (GT)n repeats in the HO-1 gene is associated with susceptibility to the development of diseases induced by oxidative stress.
To test this hypothesis, we screened …