Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population.
Methods: The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants.
Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025).
Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.
Uvod: Hronična opstruktivna bolest pluća (HOBP) jeste složeno oboljenje koje karakteriše povišen oksidativni stres. Funkcionalne varijante gena faze I i II ksenobiotičkog metabolizma mogu uticati na ravnotežu oksidanti–antioksidanti i mogu dovesti do razvoja HOBP. Cilj ove studije je bio ispi-tivanje uloge funkcionalnih genskih varijanti u genima za citohrom P450 (CYP), glutation S-transferazu (GST) i mikrozomalnu epoksidnu hidrolazu (mEH) u patogenezi HOBP u srpskoj populaciji.
Metode: U ovoj studiji analizirane su genske varijante CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null, GSTP1 Ile105Val, mEH Tyr113His i mEH His139Arg u grupi obolelih od HOBP koja je obuhvatala 122 ispitanika i kontrolnoj grupi koja je obuhvatala 100 ispitanika sa normalnom funkcijom pluća.
Rezultati: Dobijeni rezultati su pokazali da je GSTM1 null varijanta statistički značajno povišena u grupi obolelih od HOBP u poređenju sa kontrolnom grupom (61,5% i 47,0%; OR=1,80; p=0,042). Takođe, uočena je značajna razlika u zastupljenosti kombinacije genotipova GSTM1 null i GSTP1 105Val/(Val) (38,5% i 24,0%; OR=1,98; p=0,029), kao i kombinacije CYP1A1 *1A/*2A, GSTM1 null i mEH 113His/(His) (7,4% i 1,0%; OR=7,88; p=0,025).
Zaključak: Ovo su prvi podaci o ulozi genskih varijanti gena faze I i II u patogenezi HOBP u srpskoj populaciji. Rezultati dobijeni u ovoj studiji otvaraju mogućnost za detaljniju analizu uloge genetičkih faktora u HOBP na većim grupama ispitanika. Pored toga, podaci dobijeni u našoj studiji potvrđuju važnost genetičkih determinanti povezanih sa HOBP u prethodnim studijama, ali takođe otkrivaju nove genetičke faktore, koji nisu objavljeni do sada.
Keywords: COPD; candidate gene association study; genetic variation; oxidative stress.