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Variation in iron homeostasis genes between patients with acute respiratory distress syndrome and healthy controls

From the departments of Critical Care and Clinical Genomics, Imperial College School of Medicine, Royal Brompton Hospital, London, United Kingdom (Drs. Lagan, Quinlan, Melley, Pantelidis, Miss Mumby and Profs. du Bois, Welsh and Evans). Department of Cardiothoracic Surgery Royal Brompton & Harefield NHS Trust, London United Kingdom (Prof. Goldstraw). Centre for Respiratory Research, Royal Free and University College, London Medical School, Rayne Institute, London, United Kingdom (Drs. Bellingan and Hill). Histocompatibility and Immunogenetics, National Blood service, Birmingham, United Kingdom (Dr. Briggs)

t.evans{at}rbht.nhs.uk

Abstract

BackgroundAbnormal plasma and lung iron mobilization is associated with the onset and progression of ARDS and is detectable in specific at risk populations. Patients with ARDS also suffer pronounced oxidative and nitrosative stress which can be catalyzed, and thereby aggravated, by the bioavailability of redox active iron. ARDS of pulmonary and extrapulmonary origin may differ pathophysiologically and require different ventilatory strategies. Evidence suggests that genetic predisposition is relevant to the pathogenesis of ARDS. We therefore explored the hypothesis that polymorphisms from a panel of genes encoding iron metabolizing proteins determine susceptibility to ARDS.

MethodsRetrospective case-control study conducted at the adult intensive care units of two university hospitals. Patients with ARDS (n=122) and healthy controls (n=193) were genotyped. Sequence-specific primer PCR was used to genotype selected biallelic single nucleotide polymorphisms. An audit of the patient database was conducted and 104 of the 122 ARDS patients were eligible for the final data analysis.

ResultsPreliminary analysis indicated differences between ARDS and healthy controls in the incidence of polymorphism of the gene encoding ferritin light chain. Subgroup analysis indicated the prevalence of ferritin light-chain gene -3381GG homozygotes was increased in patients with ARDS of extrapulmonary origin compared to healthy controls. Secondly, a common haplotype in the heme oxygenase 2 gene was reduced in patients with ARDS compared to healthy controls and was more evident in those with ARDS of direct, or pulmonary etiology.

ConclusionsThese results provide preliminary evidence to suggest a distinction in the genetic background of the sub-populations studied, inferring that the ferritin light-chain gene genotype confers susceptibility to ARDS, whilst the heme oxygenase 2 haplotype is protective against the onset of the syndrome. Such data support further previous findings that suggest abnormalities in iron handling resulting in redox imbalance are implicated in the pathogenesis of ARDS.

Key Words: ARDS • Ferritin • Heme oxygenase • Iron Homeostasis • SNPs

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Genetics, Iron, and ALI: An Intriguing Relationship

Polly E. Parsons
Chest 2008 133: 1295-1296. [Full Text] [PDF]

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				P. E. Parsons Genetics, Iron, and ALI: An Intriguing Relationship Chest, June 1, 2008; 133(6): 1295 - 1296. [Full Text] [PDF]