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Crit Care Med. 2007 Mar;35(3):893-8.

Inhibitor kappaB-alpha haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians.

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  • 1Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.

Abstract

OBJECTIVE:

The nuclear factor (NF)-kappaB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor kappaB-alpha (NFKBIA) inhibits NF-kappaB and controls its activities. The objective was to determine whether polymorphisms in NFKBIA gene would be associated with ARDS development.

DESIGN:

Prospective cohort of adults with clinical risk factors for ARDS.

SETTING:

Hospital system.

PATIENTS:

Patients were 1,210 critically ill Caucasian patients meeting study criteria for a defined risk factor for ARDS who were enrolled and prospectively followed for 60 days; 382 had ARDS, and 828 were controls.

INTERVENTIONS:

Genetic polymorphisms in the NFKBIA promoter (-881A/G, -826C/T, -297C/T) were determined using TaqMan techniques.

MEASUREMENTS AND MAIN RESULTS:

The three polymorphisms were in Hardy-Weinberg equilibrium. No individual genotype was significantly associated with ARDS development. In contrast, haplotypes of NFKBIA were globally associated with ARDS development (p = .02, degree of freedom = 2). The frequency of haplotype GTC (-881G/-826T/-297C) was significantly higher among ARDS patients (7.4%) than that among controls (5.2%) (p = .03). Crude analysis showed that the haplotype GTC was significantly associated with higher risks of ARDS in the whole cohort compared with the common haplotype ACC (-881A/-826C/-297C) (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.03-2.09; p = .03), especially among male subjects (OR, 1.90; 95% CI, 1.20-2.97; p < .01). After adjustment for covariates, the haplotype GTC remained significantly associated with increased risk of ARDS in the whole cohort (OR, 1.66; 95% CI, 1.09-2.53; p = .02), particularly among male patients (OR, 1.98; 95% CI, 1.16-3.40; p = .02) and among subjects with direct pulmonary injury (OR, 1.75; 95% CI, 1.04-2.95; p = .04).

CONCLUSIONS:

The haplotype GTC of NFKBIA gene is associated with higher risk of ARDS in Caucasians, particularly in male patients and in patients with direct lung injury.

Comment in

PMID:
17235259
[PubMed - indexed for MEDLINE]
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