Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha1-antitrypsin deficiency

Am J Respir Cell Mol Biol. 1999 Mar;20(3):441-7. doi: 10.1165/ajrcmb.20.3.3144.

Abstract

A role for endothelial nitric oxide synthase (NOS3) in the susceptibility of individuals with alpha1-antitrypsin (alpha1AT) deficiency to destructive lung disease was evaluated. Six polymorphic sites were identified within the NOS3 gene (i.e., -924A/G, -788C/T, -691C/T, 774C/T, 894G/T, and 1998C/G). The genotype distribution was determined in 339 patients and 94 control individuals. Frequency of the 774T allele in severely affected individuals was 0.417 versus 0.269 in control subjects (P = 0.018), whereas the 894T allele frequency was 0.427 versus 0.280 in control subjects (P = 0.024). Patients with less severe lung disease had the 774T and 894T allele frequencies of 0.289 and 0.344, respectively, similar to frequencies in a control group (P > 0.3). No direct correlation between pulmonary function and five other NOS3 polymorphisms was observed. Thus, functional allelic variants that are in linkage disequilibrium with the 774C/T and 894G/T may be present in the specified genomic area. These data are consistent with a modulatory role for NOS3 in destructive lung disease associated with alpha1AT deficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Disease Susceptibility
  • Emphysema / etiology*
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Middle Aged
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type III
  • Polymorphism, Genetic
  • Sequence Analysis, DNA
  • alpha 1-Antitrypsin Deficiency / enzymology*

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III