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.
2023 Marija Stanković, Valentina Đorđević, Andrija Tomović, Ljudmila Nagorni-Obradović, Nataša Petrović-Stanojević, Mirjana Kovač, Dragica Radojković, published by CEON/CEES.