Kotze M J, van Velden D P, van Rensburg S J, Erasmus R
Department of Pathology, University of Stellenbosch , Tygerberg, South Africa .
Division of Chemical Pathology, National Health Laboratory Services (NHLS) and Faculty of Health Sciences, University of Stellenbosch , Tygerberg, South Africa .
EJIFCC. 2009 Aug 25;20(2):108-23. eCollection 2009 Aug.
Iron uptake, utilisation, release and storage occur at the gene level. Individuals with variant forms of genes involved in iron metabolism may have different requirements for iron and are likely to respond differently to the same amount of iron in the diet, a concept termed nutrigenetics. Iron deficiency, iron overload and the anemia of inflammation are the commonest iron-related disorders. While at least four types of hereditary iron overload have been identified to date, our knowledge of the genetic basis and consequences of inherited iron deficiency remain limited. The importance of genetic risk factors in relation to iron overload was highlighted with the identification of the HFE gene in 1996. Deleterious mutations in this gene account for 80-90% of inherited iron overload and are associated with loss of iron homeostasis, alterations in inflammatory responses, oxidative stress and in its most severe form, the disorder hereditary haemochromatosis (HH). Elucidation of the genetic basis of HH has led to rapid clinical benefit through drastic reduction in liver biopsies performed as part of the diagnostic work-up of affected patients. Today, detection of a genetic predisposition in the presence of high serum ferritin and transferrin saturation levels is usually sufficient to diagnose HH, thereby addressing the potential danger of inherited iron overload which starts with the same symptoms as iron deficiency, namely chronic fatigue. This review provides the scientific back-up for application of pathology supported genetic testing, a new test concept that is well placed for optimizing clinical benefit to patients with regard to iron status.
铁的摄取、利用、释放和储存发生在基因层面。参与铁代谢的基因具有不同变体形式的个体，对铁可能有不同需求，并且对饮食中相同量的铁可能有不同反应，这一概念称为营养遗传学。缺铁、铁过载和炎症性贫血是最常见的与铁相关的疾病。虽然迄今为止已确定至少四种类型的遗传性铁过载，但我们对遗传性缺铁的遗传基础和后果的了解仍然有限。1996年HFE基因的鉴定突出了遗传风险因素与铁过载的关系。该基因中的有害突变占遗传性铁过载的80 - 90%，并与铁稳态失衡、炎症反应改变、氧化应激相关，在最严重的情况下，与遗传性血色素沉着症（HH）这种疾病相关。HH遗传基础的阐明通过大幅减少作为受影响患者诊断检查一部分所进行的肝脏活检，带来了快速的临床益处。如今，在血清铁蛋白和转铁蛋白饱和度水平升高的情况下检测遗传易感性通常足以诊断HH，从而解决了遗传性铁过载的潜在危险，其最初症状与缺铁相同，即慢性疲劳。本综述为应用病理学支持的基因检测提供了科学依据，这是一种新的检测概念，非常适合优化针对铁状态患者的临床益处。
