Villette Stéphane, Kyle Janet A M, Brown Katrina M, Pickard Karen, Milne John S, Nicol Fergus, Arthur John R, Hesketh John E
Department of Biological and Nutritional Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU United Kingdom.
Blood Cells Mol Dis. 2002 Sep-Oct;29(2):174-8. doi: 10.1006/bcmd.2002.0556.
Selenium (Se) is an essential micronutrient for human health. The biological roles of the essential micronutrient Se are attributed to its presence in a range of 20-30 selenoproteins including the cytosolic and phospholipid hydroperoxide glutathione peroxidases (GPX1 and GPX4). It has been suggested that GPX4 may play a role in regulation of leukotriene biosynthesis and thus inflammation. In eukaryotes Se is incorporated into selenoproteins as the amino acid selenocysteine in a process requiring a stem-loop within the 3' untranslated region (3'UTR) of the mRNA. In this study the region of the GPX4 gene corresponding to the 3'UTR was scanned for mutations in a group of 66 volunteers. The data show a T/C variant at position 718. The distribution of this SNP in our population was 34% CC, 25% TT and 41% TC; i.e., it is in Hardy-Weinberg equilibrium. Individuals of different genotypes exhibited significant differences in the levels of lymphocyte 5-lipoxygenase total products, with C718 showing increased levels of those products compared to T718 and T/C718 (36% and 44% increases, respectively). The data suggest that the SNP718 that we have identified has functional effects and support the hypothesis that GPX4 plays a regulatory role in leukotriene biosynthesis.
硒（Se）是人体健康必需的微量营养素。必需微量营养素硒的生物学作用归因于其存在于20 - 30种硒蛋白中，包括胞质和磷脂氢过氧化物谷胱甘肽过氧化物酶（GPX1和GPX4）。有人提出，GPX4可能在白三烯生物合成的调节中发挥作用，从而影响炎症。在真核生物中，硒以硒代半胱氨酸的形式掺入硒蛋白中，这一过程需要mRNA的3'非翻译区（3'UTR）内的茎环结构。在本研究中，对66名志愿者组成的一组人群中与GPX4基因3'UTR对应的区域进行了突变扫描。数据显示在718位存在T/C变异。该单核苷酸多态性在我们人群中的分布为34% CC、25% TT和41% TC；即处于哈迪-温伯格平衡。不同基因型的个体在淋巴细胞5-脂氧合酶总产物水平上表现出显著差异，与T718和T/C718相比，C718显示这些产物水平升高（分别增加36%和44%）。数据表明，我们所鉴定的SNP718具有功能效应，并支持GPX4在白三烯生物合成中起调节作用的假说。
