PURPOSE: The inflammatory mediator interleukin-8 (IL-8) is responsible for the migration and activation of neutrophils, characteristic features of acute respiratory distress syndrome (ARDS). Previous studies showed that the A allele of a single nucleotide polymorphism in the promoter region (-251A/T, rs4073) of IL-8 was associated with increased plasma IL-8 levels. Our hypothesis was that there is an association of genotype of -251A/T with occurrence of severe ARDS in Caucasian patients who had septic shock.
METHODS: We identified patients who had severe ARDS (PaO2/FiO2 < 200 on day 1) in the vasopressin and septic shock (VASST) cohort, determined the association of the -251A/T genotype with frequency of severe ARDS and then tested for replication in a post cardiopulmonary bypass surgery (CPB) cohort. DNA was extracted from blood samples of 1,384 patients (VASST, n = 467: CPB, n = 917). Patients were genotyped for IL-8-251A/T. Associations between genotype of IL-8-251A/T and frequency of severe ARDS and differences in mortality were analyzed using the chi-squared test and log-rank test, respectively. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro.
RESULTS: The frequency of severe ARDS was greater in patients who had the AA genotype of -251A/T than patients who had the AT or TT genotypes in the VASST cohort (p=0.038) and in the CPB cohort (p=0.039). There was no significant association of -251A/T genotype with 28-day (VASST) or in-hospital (CPB) mortality in either cohort. The AA genotype -251A/T demonstrated the highest IL-8 mRNA whereas the lowest were found in TT genotypes (p=0.069).
CONCLUSIONS: The AA genotype was associated with greater IL-8 mRNA than the AT or TT genotypes. Patients who had the AA genotype of IL-8-251A/T had increased risk of severe ARDS in the Caucasians who have septic shock.
CLINICAL IMPLICATIONS: Patients who had the AA genotype of IL-8-251A/T had increased risk of severe ARDS in the Caucasians who have septic shock.
DISCLOSURE: The following authors have nothing to disclose: Petch Wacharasint, Taka-aki Nakada, John Boyd, James Russell, Keith Walley
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