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Genotypes and haplotypes of VEGF gene are associated with higher ARDS Mortality and lower VEGF plasma levels
  1. Rihong Zhai (rzhai{at}hsph.harvard.edu)
  1. Harvard School of Public Health, United States
    1. Michelle N Gong (michelle.gong{at}msnyuhealth.org)
    1. Mount Sinai School of Medicine, United States
      1. Wei Zhou (wzhou{at}hohp.harvard.edu)
      1. Harvard School of Public Health, United States
        1. Taylor B Thompson (tthompson{at}partners.org)
        1. Massachusetts General Hospital, United States
          1. Peter Kraft (pkraft{at}hsph.harvard.edu)
          1. Harvard School of Public Health, United States
            1. Li Su (lisu{at}hohp.harvard.edu)
            1. Harvard School of Public Health, United States
              1. David C Christiani (dchristi{at}hsph.harvard.edu)
              1. Harvard School of Public Health, Harvard Medical School, United States

                Abstract

                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 VEGF have been associated with VEGF production. A study was undertaken to investigate the impact of VEGF gene polymorphisms on ARDS development and clinical outcomes.

                Methods Three VEGF polymorphisms (-460C/T, +405C/G, and +936C/T) were determined in 1253 ICU patients with risk factors for ARDS. Among them 394 patients developed ARDS. Patients were followed for 60-day survival. Plasma VEGF levels were measured in 71 patients with ARDS.

                Results The +936TT (OR=4.29; 95%CI, 1.12-16.40; p=0.03) and +936CT+TT (OR=1.98; 95%CI, 1.14-3.42; p=0.01) genotypes were significantly associated with increased ARDS mortality. Plasma VEGF levels in ARDS patients with the +936CT+TT genotype (median 49pg/ml, IQR 16-98pg/ml) were significantly (p=0.02) lower than that in subjects with the +936CC genotype (median 112pg/ml, IQR 47-162pg/ml). At haplotype levels, haplotype TCT (-460T+405C+936T) was significantly associated with higher ARDS mortality (OR=2.89; 95%CI, 1.30-6.43; p=0.009). Haplotype CGT (- 460C+405G+936T) was associated less strongly with increased ARDS mortality (OR=1.90; 95%CI, 0.94-3.84; p=0.07). Lower plasma VEGF levels were correlated to 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 ARDS prognosis and inter-individual variations in circulating VEGF levels.

                • ARDS mortality
                • VEGF polymorphisms
                • plasma level

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