Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk
Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk
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DOI：
10.1093/jnci/93.23.1818
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发表时间：
2001-12-05
期刊：
影响因子：
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通讯作者：
Christiani, DC
中科院分区：
文献类型：
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作者：
Wang, LI;Miller, DP;Christiani, DC
锰超氧化物歧化酶（MnSOD）催化特定类型的活性氧物质（超氧化物自由基）歧化为过氧化氢和氧气（1）。活性氧物质的积累会破坏DNA，蛋白质和脂质，导致癌症的发生或促进（2，3）。MnSOD是线粒体中唯一已知的超氧化物清除剂，可能对抗氧化防御特别重要，因为线粒体是细胞代谢的主要场所，因此产生活性氧（4）。信号序列对于线粒体正确运输和加工蛋白质至关重要（5）。间接证据表明，MnSOD信号序列中第16位密码子（Ala 16 Val）的丙氨酸-缬氨酸多态性（5），也被描述为-9位（6），导致蛋白质螺旋结构的构象变化。这种变化可能会降低蛋白质的瓦尔同种型转运到线粒体中的效率（6，7），尽管其他研究（8，9）支持这种多态性的交替和相反的功能效应。Ala 16 Val MnSOD多态性在高加索人中很常见[频率为41%-55%（8-11）]。
Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of a specific type of reactive oxygen species, superoxide radicals, into hydrogen peroxide and oxygen (1). Accumulation of reactive oxygen species can damage DNA, proteins, and lipids, leading to the initiation or promotion of cancer (2, 3). MnSOD, the only known superoxide scavenger in mitochondria, may be particularly important for antioxidant defense because mitochondria are the major sites for cellular metabolism and hence production of reactive oxygen species (4).The signal sequence is essential for correct transport and processing of proteins by mitochondria (5). Indirect evidence suggests that the alanine-to-valine polymorphism at codon 16 (Ala16Val) in the signal sequence of MnSOD (5), also described as the–9 position (6), produces a conformational change in the helical structure of the protein. This change may decrease the efficiency of transport into mitochondria for the Val isoform of the protein (6, 7), although other studies (8, 9) support alternate and opposing functional effects of this polymorphism. The Ala16Val MnSOD polymorphism is common among Caucasians [with a frequency of 41%–55%(8–11)].