eNOS and ACE genes influence peripheral arterial disease predisposition in smokers

Elena Sticchi, Francesco Sofi, Ilaria Romagnuolo, Giovanni Pratesi, Raffaele Pulli, Carlo Pratesi, Rosanna Abbate, Cinzia Fatini

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalJournal of Vascular Surgery
Volume52
Issue number1
DOIs
Publication statusPublished - Jul 2010

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Peripheral Arterial Disease
Genes
Alleles
Haplotypes
Odds Ratio
Confidence Intervals
Gene-Environment Interaction
Nitric Oxide Synthase Type III
Disease Susceptibility
Gene Frequency
Causality
Habits
Smoking

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

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eNOS and ACE genes influence peripheral arterial disease predisposition in smokers. / Sticchi, Elena; Sofi, Francesco; Romagnuolo, Ilaria; Pratesi, Giovanni; Pulli, Raffaele; Pratesi, Carlo; Abbate, Rosanna; Fatini, Cinzia.

In: Journal of Vascular Surgery, Vol. 52, No. 1, 07.2010.

Research output: Contribution to journalArticle

Sticchi, E, Sofi, F, Romagnuolo, I, Pratesi, G, Pulli, R, Pratesi, C, Abbate, R & Fatini, C 2010, 'eNOS and ACE genes influence peripheral arterial disease predisposition in smokers', Journal of Vascular Surgery, vol. 52, no. 1. https://doi.org/10.1016/j.jvs.2010.02.021
Sticchi, Elena ; Sofi, Francesco ; Romagnuolo, Ilaria ; Pratesi, Giovanni ; Pulli, Raffaele ; Pratesi, Carlo ; Abbate, Rosanna ; Fatini, Cinzia. / eNOS and ACE genes influence peripheral arterial disease predisposition in smokers. In: Journal of Vascular Surgery. 2010 ; Vol. 52, No. 1.
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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.",
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T1 - eNOS and ACE genes influence peripheral arterial disease predisposition in smokers

AU - Sticchi, Elena

AU - Sofi, Francesco

AU - Romagnuolo, Ilaria

AU - Pratesi, Giovanni

AU - Pulli, Raffaele

AU - Pratesi, Carlo

AU - Abbate, Rosanna

AU - Fatini, Cinzia

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

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