Abstract
Respiratory disease accounts for a large proportion of emergency admissions to hospital and diseaseassociated mortality. Genetic association studies demonstrate a link between iron metabolism and pulmonary disease phenotypes. IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which has a key role in iron homeostasis. This review addresses pathways involved in iron metabolism, particularly focusing on the role of IREB2. In addition to this, environmental factors also influence phenotypic variation in respiratory disease, for example inhaled iron from cigarette smoke is deposited in the lung and causes tissue damage by altering iron homeostasis. The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer. Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome. Promising new treatments involving iron are also covered.
Highlights
Environmental risk factors, such as smoking status and air pollution, interact with genes, in order to produce pathology
Iron responsive element binding protein 2 (IREB2) is in strong linkage disequilibrium (LD) with nicotine receptor genes (CHRNA3 and 5) [5] and it is this that led IREB2 to be investigated in relation to respiratory conditions such as chronic obstructive pulmonary disease and lung cancer
The role of IREB2 and iron homeostasis was felt to be independent of the effect on lung function as there was no association between Forced expiratory volume in 1 second (FEV1) and these Single nucleotide polymorphism (SNP) [31]
Summary
Environmental risk factors, such as smoking status and air pollution, interact with genes, in order to produce pathology. * Correspondence: h.khiroya@bham.ac.uk 1School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK 2Centre for Translational Inflammation Research, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham B15 2GW, UK Full list of author information is available at the end of the article cigarette smoking, iron has been shown to alter disrupt homeostasis in the lung, making the tissue more susceptible to damage [3].
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