Inhibitor κB-α haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians

Rihong Zhai, Wei Zhou, Michelle Ng Gong, B. Taylor Thompson, Li Su, Chuling Yu, Peter Kraft, David C. Christiani

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

OBJECTIVE: The nuclear factor (NF)-κB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor κB-α (NFKBIA) inhibits NF-κB 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.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalCritical Care Medicine
Volume35
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

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Adult Respiratory Distress Syndrome
Haplotypes
Odds Ratio
Confidence Intervals
Lung Injury
Genetic Polymorphisms
Critical Illness
Genes
Genotype

Keywords

  • Acute respiratory distress syndrome
  • Genetic susceptibility
  • Haplotype
  • NFKBIA
  • Polymorphism

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Inhibitor κB-α haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians. / Zhai, Rihong; Zhou, Wei; Gong, Michelle Ng; Thompson, B. Taylor; Su, Li; Yu, Chuling; Kraft, Peter; Christiani, David C.

In: Critical Care Medicine, Vol. 35, No. 3, 03.2007, p. 893-898.

Research output: Contribution to journalArticle

Zhai, Rihong ; Zhou, Wei ; Gong, Michelle Ng ; Thompson, B. Taylor ; Su, Li ; Yu, Chuling ; Kraft, Peter ; Christiani, David C. / Inhibitor κB-α haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians. In: Critical Care Medicine. 2007 ; Vol. 35, No. 3. pp. 893-898.
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abstract = "OBJECTIVE: The nuclear factor (NF)-κB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor κB-α (NFKBIA) inhibits NF-κB 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.",
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T1 - Inhibitor κB-α haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians

AU - Zhai, Rihong

AU - Zhou, Wei

AU - Gong, Michelle Ng

AU - Thompson, B. Taylor

AU - Su, Li

AU - Yu, Chuling

AU - Kraft, Peter

AU - Christiani, David C.

PY - 2007/3

Y1 - 2007/3

N2 - OBJECTIVE: The nuclear factor (NF)-κB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor κB-α (NFKBIA) inhibits NF-κB 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.

AB - OBJECTIVE: The nuclear factor (NF)-κB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor κB-α (NFKBIA) inhibits NF-κB 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.

KW - Acute respiratory distress syndrome

KW - Genetic susceptibility

KW - Haplotype

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