ACE I allele and eNOS G allele crosstalk may have a role in chronic obstructive pulmonary disease

Clin Biochem. 2004 Nov;37(11):1037-40. doi: 10.1016/j.clinbiochem.2004.05.026.

Abstract

Background: Pulmonary hypertension, a characteristic of chronic obstructive pulmonary disease (COPD) has led us to investigate polymorphisms in angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes.

Design and methods: Sixty-six normal and 27 patients, all of whom were smokers, were screened for ACE Insertion/Deletion (I/D) and eNOS G894T and CA-repeat polymorphisms and for plasma ACE and NO levels.

Results: Elevated ACE and decreased NO levels were obtained with the pattern of II to ID to DD and GG to GT to TT conversion, respectively. Furthermore, the genotype combination of II and GG was significantly greater in controls as compared to patients (P = 0.01; OR = 2.43; 95% CI: 1.21-4.87; RR = 2.00, 1.15-3.48). The CA-repeat multialleles showed a trimodal pattern in both the groups with a frequency range of 0.0057-0.103 and 0.0208-0.1875 in the controls and patients, respectively.

Conclusions: The lower ACE and higher NO levels by virtue of the interchromosomal interaction between the I and G alleles appear to cause less vasoconstriction and increase vasodilatation that may be advantageous in the improvement of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Mutagenesis, Insertional / genetics
  • Nitric Oxide Synthase / blood
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type III
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic* / genetics
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Sequence Deletion / genetics

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • ACE protein, human
  • Peptidyl-Dipeptidase A