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.