Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS

Li Su, Rihong Zhai, Chau Chyun Sheu, Diana C. Gallagher, Michelle Ng Gong, Paula Tejera, B. Taylor Thompson, David C. Christiani

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective: Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS. Design: Unmatched, case-control study nested within a prospectively enrolled cohort. Setting: Intensive care units (ICU) of an academic medical center. Patients: About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS. Intervention: None. Measurements and results: Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (ORadjusted = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (ORadjusted = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (ORadjusted = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR adjusted = 1.90; P = 0.004). Conclusion: Common genetic variation in the Ang-2 gene may be associated with increased risk of ARDS, especially among patients with extrapulmonary injuries.

Original languageEnglish (US)
Pages (from-to)1024-1030
Number of pages7
JournalIntensive Care Medicine
Volume35
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Fingerprint

Angiopoietin-2
Adult Respiratory Distress Syndrome
Genes
Single Nucleotide Polymorphism
Wounds and Injuries
Logistic Models
Alleles
Acute Lung Injury
Capillary Permeability
Critical Illness
Haplotypes
Intensive Care Units
Case-Control Studies
Inflammation

Keywords

  • Angiopoietin-2
  • ARDS
  • Genetic susceptibility
  • Haplotype
  • Molecular epidemiology
  • Tagging single nucleotide polymorphism

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Su, L., Zhai, R., Sheu, C. C., Gallagher, D. C., Gong, M. N., Tejera, P., ... Christiani, D. C. (2009). Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS. Intensive Care Medicine, 35(6), 1024-1030. https://doi.org/10.1007/s00134-009-1413-8

Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS. / Su, Li; Zhai, Rihong; Sheu, Chau Chyun; Gallagher, Diana C.; Gong, Michelle Ng; Tejera, Paula; Thompson, B. Taylor; Christiani, David C.

In: Intensive Care Medicine, Vol. 35, No. 6, 06.2009, p. 1024-1030.

Research output: Contribution to journalArticle

Su, L, Zhai, R, Sheu, CC, Gallagher, DC, Gong, MN, Tejera, P, Thompson, BT & Christiani, DC 2009, 'Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS', Intensive Care Medicine, vol. 35, no. 6, pp. 1024-1030. https://doi.org/10.1007/s00134-009-1413-8
Su, Li ; Zhai, Rihong ; Sheu, Chau Chyun ; Gallagher, Diana C. ; Gong, Michelle Ng ; Tejera, Paula ; Thompson, B. Taylor ; Christiani, David C. / Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS. In: Intensive Care Medicine. 2009 ; Vol. 35, No. 6. pp. 1024-1030.
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abstract = "Objective: Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS. Design: Unmatched, case-control study nested within a prospectively enrolled cohort. Setting: Intensive care units (ICU) of an academic medical center. Patients: About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS. Intervention: None. Measurements and results: Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (ORadjusted = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (ORadjusted = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (ORadjusted = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR adjusted = 1.90; P = 0.004). Conclusion: Common genetic variation in the Ang-2 gene may be associated with increased risk of ARDS, especially among patients with extrapulmonary injuries.",
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AU - Su, Li

AU - Zhai, Rihong

AU - Sheu, Chau Chyun

AU - Gallagher, Diana C.

AU - Gong, Michelle Ng

AU - Tejera, Paula

AU - Thompson, B. Taylor

AU - Christiani, David C.

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N2 - Objective: Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS. Design: Unmatched, case-control study nested within a prospectively enrolled cohort. Setting: Intensive care units (ICU) of an academic medical center. Patients: About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS. Intervention: None. Measurements and results: Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (ORadjusted = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (ORadjusted = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (ORadjusted = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR adjusted = 1.90; P = 0.004). Conclusion: Common genetic variation in the Ang-2 gene may be associated with increased risk of ARDS, especially among patients with extrapulmonary injuries.

AB - Objective: Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS. Design: Unmatched, case-control study nested within a prospectively enrolled cohort. Setting: Intensive care units (ICU) of an academic medical center. Patients: About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS. Intervention: None. Measurements and results: Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (ORadjusted = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (ORadjusted = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (ORadjusted = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR adjusted = 1.90; P = 0.004). Conclusion: Common genetic variation in the Ang-2 gene may be associated with increased risk of ARDS, especially among patients with extrapulmonary injuries.

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KW - Haplotype

KW - Molecular epidemiology

KW - Tagging single nucleotide polymorphism

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