AA genotype of IL-8 -251A/T is associated with low PaO(2) /FiO(2) in critically ill patients and with increased IL-8 expression.

Summary of "AA genotype of IL-8 -251A/T is associated with low PaO(2) /FiO(2) in critically ill patients and with increased IL-8 expression."

SUMMARY AT A
GLANCE:
This study demonstrated that variation in the IL-8 promoter gene region was associated with increased risk of impaired oxygenation and prolonged mechanical ventilation in the critically ill patients. One possible mechanism may be because of altered IL-8 mRNA expression
ABSTRACT:
Background and Objective:  Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS) and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) -251A/T in its promoter region.We hypothesized that IL-8 -251A/T SNP is associated with PaO(2) /FiO(2) in critically ill patients. Methods:  We conducted genetic-association studies in intensive care units at academic teaching centers using a derivation septic shock cohort (VASST, n=467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n=739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 -251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO(2) /FiO(2) < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. Results:  The frequency of the patients with PaO(2) /FiO(2) <200 was significant greater in patients who had the AA genotype of -251A/T than patients who had the AT or TT genotypes in both VASST (AA =60.8% vs. AT and TT =53.8% and 48.0%, p=0.038) and the CPB cohort (AA =37.0% vs. AT and TT =27.0% and 26.0%, p=0.039). Patients having the AA genotype had a higher probability to remaining on mechanical ventilation (p=0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype (p=0.022). Conclusions:  Caucasian critically ill patients who had the AA genotype of IL-8 -251A/T had an increased risk of PaO(2) /FiO(2) <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Affiliation

University of British Columbia, Critical Care Research Laboratories, Institute for Heart+Lung Health, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.

Journal Details

This article was published in the following journal.

Name: Respirology (Carlton, Vic.)
ISSN: 1440-1843
Pages:

Links

• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22897124
• DOI: http://dx.doi.org/10.1111/j.1440-1843.2012.02244.x