title: Variation in iron homeostasis genes between patients with ARDS and healthy control subjects.
abstract: BACKGROUND
  Abnormal 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 have pronounced oxidative and nitrosative stress that 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.
  
  
  METHODS
  Retrospective case-control study conducted at the adult ICUs of two university hospitals. Patients with ARDS (n = 122) and healthy control subjects (n = 193) were genotyped. Sequence-specific primer polymerase chain reaction 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.
  
  
  RESULTS
  Preliminary analysis indicated differences between ARDS and healthy control subjects 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 control subjects. Secondly, a common haplotype in the heme oxygenase 2 gene was reduced in patients with ARDS compared to healthy control subjects and was more evident in those with ARDS of direct or pulmonary etiology.
  
  
  CONCLUSIONS
  These results provide preliminary evidence to suggest a distinction in the genetic background of the subpopulations studied, inferring that the ferritin light-chain gene genotype confers susceptibility to ARDS, while 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.
authors.affiliation: Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Lagan
authors.affiliation: Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Quinlan
authors.affiliation: Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mumby
authors.affiliation: Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Melley
authors.affiliation: Department of Cardiothoracic Surgery, Royal Brompton & Harefield NHS Trust, London.
authors.forename: Peter
authors.initials: P
authors.lastname: Goldstraw
authors.affiliation: Centre for Respiratory Research, Royal Free and University College, London Medical School, Rayne Institute, London.
authors.forename: Geoff J
authors.initials: GJ
authors.lastname: Bellingan
authors.affiliation: Centre for Respiratory Research, Royal Free and University College, London Medical School, Rayne Institute, London.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hill
authors.affiliation: Histocompatibility and Immunogenetics, National Blood Service, Birmingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.affiliation: Clinical Genomics Group, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Pantelidis
authors.affiliation: Clinical Genomics Group, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.affiliation: Clinical Genomics Group, Imperial College School of Medicine, Royal Brompton Hospital, London.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Welsh
authors.affiliation: Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, London. Electronic address: t.evans@rbht.nhs.uk.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001052:Apoferritins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000502:physiology; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020641:Polymorphism, Single Nucleotide; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D012189:Retrospective Studies; D014131:Trace Elements / Q000378:metabolism*
chemical_list: D014131:Trace Elements; D001052:Apoferritins; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2