ACUTE LUNG INJURY

Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower VEGF plasma levels in patients with ARDS

R Zhai¹, M N Gong², W Zhou¹, T B Thompson³, P Kraft⁴, L Su¹, D C Christiani^1,3

¹ Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
² Division of Pulmonary and Critical Care Medicine, Mount Sinai School of Medicine, New York, USA
³ Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
⁴ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

Correspondence to:
Dr David C Christiani
Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA; dchristi{at}hsph.harvard.edu

Background: Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS). Vascular endothelial growth factor (VEGF) plays a critical role in endothelial destruction and angiogenesis. Genetic variations of the VEGF gene have been associated with VEGF production. A study was undertaken to investigate the impact of VEGF gene polymorphisms on the clinical outcomes of ARDS.

Methods: Three VEGF polymorphisms (–460C/T, +405C/G and +936C/T) were determined in 1253 patients in an intensive care unit with risk factors for ARDS, 394 of whom developed ARDS. Patients were followed for assessment of 60 day survival. Plasma VEGF levels were measured in 71 patients with ARDS.

Results: The +936TT (OR 4.29, 95% CI 1.12 to 16.40, p = 0.03) and +936CT+TT (OR 1.98, 95% CI 1.14 to 3.42, p = 0.01) genotypes were significantly associated with increased mortality from ARDS. Plasma VEGF levels in patients with ARDS with the +936CT+TT genotype were significantly lower than in subjects with the +936CC genotype (median 49 (IQR 16–98) pg/ml vs 112 (IQR 47–162) pg/ml, p = 0.02). At the haplotype level, haplotype TCT (–460T+405C+936T) was significantly associated with a higher rate of mortality (OR 2.89, 95% CI 1.30 to 6.43, p = 0.009) and haplotype CGT (–460C+405G+936T) was associated less strongly with increased mortality (OR 1.90, 95% CI 0.94 to 3.83, p = 0.07) in patients with ARDS. Lower plasma VEGF levels were correlated with the probability of haplotype CGT (coefficient = –0.26, p<0.05), but the same trend of correlation was not significant to haplotype TCT.

Conclusions: VEGF polymorphisms may contribute to the prognosis and inter-individual variations in circulating VEGF levels in patients with ARDS.

Abbreviations: ARDS, acute respiratory distress syndrome; SNP, single nucleotide polymorphism; VEGF, vascular endothelial growth factor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Airwaves

Wisia Wedzicha
Thorax 2007 62: 653. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Zhai, R, Sheu, C C, Su, L, Gong, M N, Tejera, P, Chen, F, Wang, Z, Convery, M P, Thompson, B T, Christiani, D C (2009). Serum bilirubin levels on ICU admission are associated with ARDS development and mortality in sepsis. Thorax 64: 784-790 [Abstract] [Full Text]  
• Medford, A. R. L., Godinho, S. I. H., Keen, L. J., Bidwell, J. L., Millar, A. B. (2009). Relationship Between Vascular Endothelial Growth Factor + 936 Genotype and Plasma/Epithelial Lining Fluid Vascular Endothelial Growth Factor Protein Levels in Patients With and at Risk for ARDS. Chest 136: 457-464 [Abstract] [Full Text]  
• Gao, L., Barnes, K. C. (2009). Recent advances in genetic predisposition to clinical acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L713-L725 [Abstract] [Full Text]  
• Heist, R. S., Christiani, D. C. (2008). In Reply. JCO 26: 3290-3290 [Full Text]  
• Patel, M., Ailawadhi, S., Hernandez-Ilizaliturri, F., Wilding, G. E. (2008). Vascular Endothelial Growth Factor Polymorphisms in Early-Stage Non-Small-Cell Lung Cancer. JCO 26: 3289-3290 [Full Text]  
• Heist, R. S., Zhai, R., Liu, G., Zhou, W., Lin, X., Su, L., Asomaning, K., Lynch, T. J., Wain, J. C., Christiani, D. C. (2008). VEGF Polymorphisms and Survival in Early-Stage Non-Small-Cell Lung Cancer. JCO 26: 856-862 [Abstract] [Full Text]  
• Lagan, A. L., Melley, D. D., Evans, T. W., Quinlan, G. J. (2008). Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L161-L174 [Abstract] [Full Text]  
• Zhai, R., Liu, G., Zhou, W., Su, L., Heist, R. S., Lynch, T. J., Wain, J. C., Asomaning, K., Lin, X., Christiani, D. C. (2008). Vascular Endothelial Growth Factor Genotypes, Haplotypes, Gender, and the Risk of Non-Small Cell Lung Cancer. Clin. Cancer Res. 14: 612-617 [Abstract] [Full Text]