title: eNOS and ACE genes influence peripheral arterial disease predisposition in smokers.
abstract: OBJECTIVE
  Several biologic mediators and genetic predisposing factors may contribute to the development of peripheral arterial disease (PAD). The eNOS gene, encoding for endothelial nitric oxide synthase, has been proposed as a candidate gene in the predisposition to the disease. In this study, we evaluated the role of eNOS-786T>C, -894G>T and 4a/4b polymorphisms as markers of PAD per se and in the presence of the ACE D allele in patients previously investigated.
  
  
  METHODS
  We analyzed 281 consecutive patients (220 men, 61 women; median age, 72 years) with PAD and 562 healthy controls, comparable for sex and age.
  
  
  RESULTS
  eNOS-786C, but not -894T and 4a, allele frequency was significantly higher in PAD patients than in controls (P = .03). An association with the predisposition to PAD was found for the eNOS-786C allele (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.11-2.09; P = .009) and the eNOS -786C/4a haplotype (OR, 1.41; 95% CI, 1.02-1.94, P = .04) at univariate analysis but not after adjustment for traditional risk factors. When smoking habit was considered, we observed that eNOS-786C/4a haplotype, but not the eNOS-786C allele, influenced PAD predisposition after adjustment for traditional risk factors in smokers (OR, 2.71; 95% CI, 1.38-5.30; P = .004). The eNOS-786C and eNOS-786C/4a haplotype did not modify the susceptibility to PAD in patients carrying the ACE D allele. Nevertheless, the presence of the eNOS-786C/4a haplotype increased PAD predisposition in smokers also carrying ACE D allele (OR, 2.71 to 3.79; P > .05 for interaction).
  
  
  CONCLUSIONS
  This study demonstrated an association between eNOS and ACE genes in increasing PAD susceptibility in smokers, thus providing evidence for a gene-environment interaction in modulating predisposition to the disease.
authors.affiliation: Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Sofi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Romagnuolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pratesi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pulli
authors.forename: Carlo
authors.initials: C
authors.lastname: Pratesi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016491:Peripheral Vascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A