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Original

Endothelial Dysfunction in Patients with Asthma: The Role of Polymorphisms of ACE and Endothelial NOS Genes

, M.D., , M.D., , Ph.D., , M.D., , Ph.D., , M.D. & , M.D. show all
Pages 159-166 | Published online: 26 Aug 2009
 

Abstract

Objectives. Polymorphisms of the angiotensin converting enzyme (ACE) and endothelial nitric oxide (eNOS) genes have been implicated in asthma pathogenesis. Angiotensin II and NO have important roles in maintaining vascular tone. In this study, the relationship between endothelial dysfunction and ACE and eNOS gene polymorphisms was investigated in patients with asthma. Methods. This cross‐sectional, controlled study was conducted at the Yedikule Chest Disease Hospital and Cardiology Center in a University Hospital. Forty‐nine patients with asthma (18 male, 31 female; mean age: 33 ± 12 years) and 49 age‐ and sex‐matched healthy controls (20 male, 29 female; mean age: 30 ± 8 years) were included. Pulmonary function tests and flow‐mediated dilatation of the brachial artery [endothelium dependent dilatation (EDD)] were examined by high‐resolution ultrasonography. The ACE and eNOS genotypes were determined by PCR. Results. Asthma patients showed lower EDD (12 ± 6% vs. 22 ± 6%, p < 0.001) as compared to controls. The EDD was correlated with both predicted value of FEV1 (r = 0.31, p = 0.04) and predicted value of FVC (r = 0.37, p = 0.013). Conversely, EDD values in patients with moderate asthma were significantly lower than those in patients with mild asthma (10.1 ± 5.2% vs. 14.1 ± 5.7%, p = 0.017). However, the ACE and eNOS genotype distribution was not significantly different between controls and asthma groups. Furthermore, EDD was not associated with both gene polymorphism of ACE and eNOS. Conclusion. Patients with asthma have decreased vasodilatatory response to shear stress (EDD). Decreased EDD is correlated with the severity of asthma, but not with the distribution of ACE and eNOS genotypes.

Abbreviations
ACE:=

Angiotensin converting enzyme

AII:=

Angiotensin II

DD:=

Homozygous deletion type allele

DI:=

Heterozygote deletion‐insertion type allele

EDD:=

Endothelium dependent dilatation

eNOS:=

Endothelial nitric oxide synthase

FVC:=

Forced vital capacity

FEV1:=

Forced expiratory volume 1 second (FEV1)

FEF25%–75%:=

Forced expiratory flow at 25% to 75% of FVC

II:=

Homozygous insertion type allele

NO:=

Nitric oxide

PEFR:=

Peak expiratory flow rate

VC:=

Vital capacity

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