Méplan Catherine
School of Biomedical Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Nutrients. 2015 May 15;7(5):3621-51. doi: 10.3390/nu7053621.
Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.
机制研究数据显示，硒（Se）和硒蛋白在多因素疾病中已知会发生改变的生物途径中发挥关键作用，如细胞维持、对氧化应激的反应以及正确的蛋白质折叠。尽管流行病学研究表明，低硒摄入量与多种慢性疾病风险增加有关，但补充试验结果却令人困惑，这表明其他遗传因素可能会影响硒与健康之间的关系。遗传数据支持这一假设，因为多种慢性疾病，尤其是癌症的风险与一些改变硒代谢、硒蛋白合成或活性的单核苷酸多态性（SNP）有关。研究发现，硒蛋白基因中的SNP、相关分子途径中的SNP与硒状态生物标志物之间的相互作用会进一步调节SNP所携带的遗传风险。综合来看，营养基因组学方法揭示了一些硒蛋白的潜在影响，以及基因变异与硒状态之间复杂相互作用在几种慢性疾病病因学中的影响。本综述在硒蛋白功能和流行病学调查的背景下讨论了这些遗传关联的结果，并强调在未来研究中需要评估硒状态、环境压力以及多个或单个SNP对疾病风险的综合影响。
