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. 2023 Jan 20;42(1):94-104.
doi: 10.5937/jomb0-34017.

Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease

Marija Stanković  1 , Valentina Đorđević  1 , Andrija Tomović  2 , Ljudmila Nagorni-Obradović  3 , Nataša Petrović-Stanojević  4 , Mirjana Kovač  3 , Dragica Radojković  1
Affiliations

Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease

Marija Stanković et al. J Med Biochem. .

Abstract
in English, Serbian

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder with unexplained heritability. Interactions of genetic and environmental factors are thought to be crucial in COPD. So, we aim to examine interactions of the endothelial nitric oxide synthase (eNOS) and angiotensin converting enzyme (ACE) genes and cigarette smoking in COPD.

Methods: The eNOS G 894T and ACE ID variants were analyzed in 122 COPD patients and 200 controls from Serbia. The effect of the variants on COPD was assessed by logistic regression. Interactions between eNOS, ACE and cigarette smoking in COPD were evaluated using a case-control model. Interaction between the genes was analyzed in silico.

Results: No effect of the eNOS G 894T and ACE ID variants on COPD was found in our study. Gene-gene interaction between the eN OS T T and A CE D was identified (p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environment interactions between the eNOS T and cigarette smoking (p=0.013), and the ACE II and cigarette smoking (p=0.009) were detected in COPD in our study.

Conclusions: This is the first research to reveal interactions of the eNOS and ACE genes and cigarette smoking in COPD progressing our understanding of COPD heritability and contributing to the development of appropriate treatments.

Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom. Smatra se da su interakcije genetskih i spoljašnjih faktora kljucne u HOBP Stoga je naš cilj bio da ispitamo interakcije gena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima u HOBP.

Metode: eNOS G 894T i ACE ID varijante su analizirane kod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticaj varijanti na HOBP je ispitan logističkom regresijom. Interakcije između eNOS, ACE i duvanskog dima u HOBP su ispitane korišćenjem modela slučaj-kontrola. Interakcija između gena je analizirana in silico.

Rezultati: Prema ovoj studiji eNOS G 894T i ACE ID varijante nemaju uticaj na HOBP GEN-gen interakcija između eNOS T T i ACE D je identifikovana (p=0,033) u HOBP Ova interakcija se ostvaruje u okviru složene mreže biohemijskih puteva. GEN-sredina interakcije između eNOS T i duvanskog dima (p=0,013), i ACE II i duvanskog dima (p=0,009) su detektovane u HOBP u ovoj studiji.

Zaključak: Ovo je prvo istraživanje u kome su otkrivene interakcije između eNOS i ACE gena i duvanskog dima u HOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.

Keywords: ACE; COPD; cigarette smoking; eNOS; gene-environment interaction; genegene interaction.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: The authors stated that they have no conflicts of interest regarding the publication of this article.

Figures

Figure 1
Figure 1. The biochemical pathways of eNOS and ACE interaction.
Figure 1 eNOS and ACE (black circles) interact within the network of biochemical pathways (white circles). The network is based on physical, genetic and predicted interactions, pathways and co-localisation using a web-based tool GeneMANIA. The simplest interaction is realised by caveolin-1, GUCY1A1 and BDKRB2 (grey circles). The larger size circles indicate the genes with the greater degree in the network.
ACE-angiotensin converting enzyme, ACE2-angiotensin converting enzyme 2, AGTR2-angiotensin II receptor type 2, AKT1-AKT serine/threonine kinase 1, ATP6AP2-ATPase H+ transporting accessory protein 2, BDKRB2-bradykinin receptor B2, CAV1-caveolin-1, CAV3-caveolin-3, EDNRB-endothelin receptor type B, EIF4G2-eukaryotic translation initiation factor 4 gamma 2, eNOS-endothelial nitric oxide synthase, GUCY1A2-guanylate cyclase 1 soluble subunit alpha 2, GUCY1A1-guanylate cyclase 1 soluble subunit alpha 1, GUCY1B1-guanylate cyclase 1 soluble subunit beta 1, HSP90AB1-heat shock protein 90 alpha family class B member 1, LYPLA1-lysophospholipase 1, MYH9-myosin heavy chain 9, NOSIP-nitric oxide synthase interacting protein, NOSTRIN-nitric oxide synthase trafficking, NSMAF-neutral sphingomyelinase activation associated factor, REN-renin, ZDHHC21-zinc finger DHHC-type containing 21.
Figure 2
Figure 2. Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease.
Figure 2 Gene-gene interaction between the eNOS TT and ACE D showed risk (OR=4.21, p=0.033) for the development of COPD. Carriers of double risk genotype, the eNOS TT and ACE DD were more frequent in COPD patients than in NLF and VBD controls (4.1% versus 0.0%). Gene-environment interactions between the eNOS 894T and cigarette smoking (OR=3.37, p=0.013) and between the ACE II and cigarette smoking (OR=4.21, p=0.009) showed risk for the occurrence of COPD.
ACE-angiotensin converting enzyme, eNOS-endothelial nitric oxide synthase, COPD-chronic obstructive pulmonary disease.
See this image and copyright information in PMC

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