title: Heme oxygenase 1 polymorphisms and plasma concentrations in critically ill patients.
abstract: Heme oxygenase 1 (HO-1) is a cytoprotective enzyme upregulated by various critical illness-related stress stimuli. We investigated the association of HO-1 gene polymorphisms and plasma concentrations with the outcome of critically ill patients in a prospective cohort study of 231 critically ill patients admitted to tertiary care medical and medical-surgical intensive care units. Blood samples were collected on days 1, 2, and 3 to 4 in the intensive care unit. The HO-1 plasma concentration was measured in serial samples, and HO-1 single nucleotide polymorphisms, -413A/T and +99G/C, and HO-1 promoter GTn repeat length polymorphism were determined. The +99C and long GTn alleles were in perfect linkage disequilibrium, and the -413T/GT(L)/+99C haplotype had significant independent effect on first-day HO-1 plasma concentrations in linear regression analysis (P = 0.03) and associated with lower HO-1 plasma levels. Furthermore, -413T/GT(L)/+99C haplotype associated with a lower frequency of multiple-organ dysfunction compared with other haplotypes (P = 0.017). The HO-1 plasma concentrations of study patients were significantly higher than the values of healthy controls at all time points (P < 0.001), and the first-day plasma HO-1 levels were independently associated with the Sequential Organ Failure Assessment score (P = 0.001). In conclusion, the HO-1 -413T/GT(L)/+99C haplotype is associated with HO-1 plasma levels and the frequency of multiple-organ dysfunction in critically ill patients. The HO-1 plasma concentrations are significantly increased among critically ill patients and associated with the degree of organ dysfunction.
authors.affiliation: Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Saukkonen
authors.forename: Päivi
authors.initials: P
authors.lastname: Lakkisto
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kaunisto
authors.forename: Marjut
authors.initials: M
authors.lastname: Varpula
authors.forename: Liisa-Maria
authors.initials: LM
authors.lastname: Voipio-Pulkki
authors.forename: Tero
authors.initials: T
authors.lastname: Varpula
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.forename: Kari
authors.initials: K
authors.lastname: Pulkki
mesh_terms: D000368:Aged; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D051547:Heme Oxygenase-1