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Copyright ©ERS Journals Ltd 2005
–308GA and TNFB polymorphisms in acute respiratory distress syndrome
1 Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Mount Sinai School of Medicine, New York, 2 Environmental Health Dept (Occupational Health Program), and 3 Dept of Biostatistics, Harvard School of Public Health, and 4 Pulmonary and Critical Care Unit, Dept of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
CORRESPONDENCE: D. C. Christiani, Harvard School of Public Health, 665 Huntington Avenue, Boston MA, 02115, USA. Fax: 1 6174323441. E-mail: dchristi@hsph.harvard.edu
Keywords: Acute respiratory distress syndrome, genetic susceptibility, tumour necrosis factor
Received: January 3, 2005
Accepted May 17, 2005
The –308GA and TNFB1/2 polymorphisms of the tumour necrosis factor genes have been associated with increased susceptibility to, and mortality in sepsis, although, prior studies are not consistent. Their role in acute respiratory distress syndrome (ARDS) has not been evaluated. The current authors hypothesised that the –308A allele and TNFB22 genotype would be associated with increased susceptibility to, and mortality in ARDS.
The above hypothesis was investigated in a nested case-control study of 441 Caucasian controls and 212 cases admitted to an intensive care unit with sepsis, trauma, aspiration or hyper-transfusions.
The –308A and TNFB1 alleles were in linkage disequilibrium. These polymorphisms were not associated with ARDS susceptibility on crude analysis. On subgroup analyses, they were associated with either increased or decreased odds of developing ARDS depending on whether the clinical risk for ARDS results in direct or indirect pulmonary injury. The –308A allele was associated with increased 60-day mortality in ARDS, with the strongest association found among younger patients. There was no association between the TNFB polymorphism and ARDS mortality.
The –308GA, but not the TNFB12, polymorphism was associated with increased mortality in acute respiratory distress syndrome, but their association with acute respiratory distress syndrome susceptibility depended on the site of injury predisposing to acute respiratory distress syndrome.
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