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Association of (CCTTT)10, a nitric oxide synthase 2 promoter polymorphism, with death due to acute lung injury

Introduction

Nitric oxide via inducible nitric oxide synthase (NOS2) is believed to be a molecule central to the pathogenesis of acute lung injury (ALI). (CCTTT) n , a polymorphism within the NOS2 gene promoter, has been associated with outcome in some pathologies. The study objective was to investigate the frequency of the (CCTTT) n alleles in patients with ALI and to determine whether their occurrence affects the outcome of ALI.

Methods

A monocenter cohort study conducted from June 2006 to February 2007 in a medical ICU in a university hospital. Two hundred and sixty-four patients were included in the cohort, and 112 patients with ALI. The main outcome measures were the frequency of the (CCTTT) n alleles among patients with ALI and among those who died.

Results

The polymorphism frequencies of the survivors in the cohort and the patients with ALI differed only at the (CCTTT)10 allele (10 repetitions) (83% vs 17% in the survivor and nonsurvivor patients in the cohort, respectively, P = 0.034; 90% vs 10% in the survivor and nonsurvivor patients with ALI, respectively, P = 0.026). The frequency of the (CCTTT)10 allele among the cohort and patients with ALI was 15% and 13%, respectively, consistent with the Caucasian population frequency. A multiple logistic regression analysis showed that patients with the (CCTTT)10 allele had a 0.5-fold risk of death in the cohort (P = 0.035) and a 0.22-fold risk of death in the ALI group (P = 0.029). A Kaplan–Meier study showed that survival was significantly enhanced among patients with ALI who had the (CCTTT)10 allele (P = 0.006).

Conclusion

The (CCTTT)10 allele, a NOS2 promoter polymorphism, is strongly associated with survival in ALI.

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Perez, D., Manzon, C., Navellou, J. et al. Association of (CCTTT)10, a nitric oxide synthase 2 promoter polymorphism, with death due to acute lung injury. Crit Care 12, P463 (2008). https://doi.org/10.1186/cc6684

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Keywords

  • Nitric Oxide
  • Logistic Regression Analysis
  • Gene Promoter
  • Acute Lung Injury
  • Caucasian Population