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Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis

Genetički polimorfizmi paraoksonaze 1 i podložnost aterogenezi

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2013
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Authors
Grubiša, Ivana
Otašević, Petar
Dimković, Nada
Nedeljković, Ivana
Toljić, Boško
Vučinić, Nada
Article (Published version)
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Abstract
Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genoty...ping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.

Uvod. Paraoksonaza 1 (PON1) je multifunkcionalni enzim koji je vezan za lipoproteine visoke gustine (HDL). To je ćelijski antioksidans koji hidrolizuje oksidovane makromolekule, naročito oksidovane lipoproteine niske gustine (ox-LDL). Smatra se da povišeni oksidativni stres igra ključnu ulogu u inicijaciji i propagaciji ateroskleroze, pa su polimorfizmi u kodirajućem (Q192R i L55M) i promotorskom (C(-107)T) regionu gena pon1, koji su odgovorni za katalitičku efikasnost, aktivnost i nivo enzima, od velikog interesa kao potencijalni markeri osetljivosti na aterogenezu. Cilj rada. Cilj ove studije je bio da se ispita moguća povezanost varijanti gena pon1 i kliničkih manifestacija ateroskleroze i oksidativnog stresa. Metode rada. Analizirano je 60 bolesnika s angiografski dokumentovanim manifestacijama ateroskleroze i 100 zdravih ispitanika. Genomska DNK je izolovana iz ćelija periferne krvi, a genotipizacija je urađena primenom reakcije lančane polimeraze, posle koje je urađena analiza du...žine restrikcionih fragmenata (tzv. PCR-RFLP analiza). Rezultati. Učestalosti alela i genotipova tri ispitivana polimorfizma nisu pokazale značajne razlike između ispitanika obolelih od ateroskleroze i zdravih osoba. Dobijeni rezultati ne ukazuju na povezanost analiziranih varijanti gena pon1 i oksidativnog stresa i aterogeneze. Zaključak. Ovi polimorfizmi se ne mogu smatrati faktorima rizika za razvoj ateroskleroze u srpskoj populaciji. Potrebna je studija sa većim brojem ispitanika, kako bi se utvrdio mogući doprinos varijanti gena pon1 na nastanak kardiovaskularnih oboljenja u čijoj osnovi je ateroskleroza.

Keywords:
paraoxonase 1 / gene polymorphisms / oxidative stress / atherogenesis / paraoksonaza 1 / genetički polimorfizmi / oksidativni stres / aterogeneza
Source:
Srpski arhiv za celokupno lekarstvo, 2013, 141, 9-10, 629-633
Publisher:
  • Srpsko lekarsko društvo, Beograd
Funding / projects:
  • Genetic control and molecular mechanisms in malignant, inflammatory and developmental pathologies of the orofacial region (RS-175075)

DOI: 10.2298/SARH1310629G

ISSN: 0370-8179

WoS: 000326995300009

Scopus: 2-s2.0-84911028041
[ Google Scholar ]
12
11
URI
https://smile.stomf.bg.ac.rs/handle/123456789/1800
Collections
  • Radovi istraživača
Institution/Community
Stomatološki fakultet
TY  - JOUR
AU  - Grubiša, Ivana
AU  - Otašević, Petar
AU  - Dimković, Nada
AU  - Nedeljković, Ivana
AU  - Toljić, Boško
AU  - Vučinić, Nada
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1800
AB  - Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.
AB  - Uvod. Paraoksonaza 1 (PON1) je multifunkcionalni enzim koji je vezan za lipoproteine visoke gustine (HDL). To je ćelijski antioksidans koji hidrolizuje oksidovane makromolekule, naročito oksidovane lipoproteine niske gustine (ox-LDL). Smatra se da povišeni oksidativni stres igra ključnu ulogu u inicijaciji i propagaciji ateroskleroze, pa su polimorfizmi u kodirajućem (Q192R i L55M) i promotorskom (C(-107)T) regionu gena pon1, koji su odgovorni za katalitičku efikasnost, aktivnost i nivo enzima, od velikog interesa kao potencijalni markeri osetljivosti na aterogenezu. Cilj rada. Cilj ove studije je bio da se ispita moguća povezanost varijanti gena pon1 i kliničkih manifestacija ateroskleroze i oksidativnog stresa. Metode rada. Analizirano je 60 bolesnika s angiografski dokumentovanim manifestacijama ateroskleroze i 100 zdravih ispitanika. Genomska DNK je izolovana iz ćelija periferne krvi, a genotipizacija je urađena primenom reakcije lančane polimeraze, posle koje je urađena analiza dužine restrikcionih fragmenata (tzv. PCR-RFLP analiza). Rezultati. Učestalosti alela i genotipova tri ispitivana polimorfizma nisu pokazale značajne razlike između ispitanika obolelih od ateroskleroze i zdravih osoba. Dobijeni rezultati ne ukazuju na povezanost analiziranih varijanti gena pon1 i oksidativnog stresa i aterogeneze. Zaključak. Ovi polimorfizmi se ne mogu smatrati faktorima rizika za razvoj ateroskleroze u srpskoj populaciji. Potrebna je studija sa većim brojem ispitanika, kako bi se utvrdio mogući doprinos varijanti gena pon1 na nastanak kardiovaskularnih oboljenja u čijoj osnovi je ateroskleroza.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis
T1  - Genetički polimorfizmi paraoksonaze 1 i podložnost aterogenezi
VL  - 141
IS  - 9-10
SP  - 629
EP  - 633
DO  - 10.2298/SARH1310629G
ER  - 
@article{
author = "Grubiša, Ivana and Otašević, Petar and Dimković, Nada and Nedeljković, Ivana and Toljić, Boško and Vučinić, Nada",
year = "2013",
abstract = "Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases., Uvod. Paraoksonaza 1 (PON1) je multifunkcionalni enzim koji je vezan za lipoproteine visoke gustine (HDL). To je ćelijski antioksidans koji hidrolizuje oksidovane makromolekule, naročito oksidovane lipoproteine niske gustine (ox-LDL). Smatra se da povišeni oksidativni stres igra ključnu ulogu u inicijaciji i propagaciji ateroskleroze, pa su polimorfizmi u kodirajućem (Q192R i L55M) i promotorskom (C(-107)T) regionu gena pon1, koji su odgovorni za katalitičku efikasnost, aktivnost i nivo enzima, od velikog interesa kao potencijalni markeri osetljivosti na aterogenezu. Cilj rada. Cilj ove studije je bio da se ispita moguća povezanost varijanti gena pon1 i kliničkih manifestacija ateroskleroze i oksidativnog stresa. Metode rada. Analizirano je 60 bolesnika s angiografski dokumentovanim manifestacijama ateroskleroze i 100 zdravih ispitanika. Genomska DNK je izolovana iz ćelija periferne krvi, a genotipizacija je urađena primenom reakcije lančane polimeraze, posle koje je urađena analiza dužine restrikcionih fragmenata (tzv. PCR-RFLP analiza). Rezultati. Učestalosti alela i genotipova tri ispitivana polimorfizma nisu pokazale značajne razlike između ispitanika obolelih od ateroskleroze i zdravih osoba. Dobijeni rezultati ne ukazuju na povezanost analiziranih varijanti gena pon1 i oksidativnog stresa i aterogeneze. Zaključak. Ovi polimorfizmi se ne mogu smatrati faktorima rizika za razvoj ateroskleroze u srpskoj populaciji. Potrebna je studija sa većim brojem ispitanika, kako bi se utvrdio mogući doprinos varijanti gena pon1 na nastanak kardiovaskularnih oboljenja u čijoj osnovi je ateroskleroza.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis, Genetički polimorfizmi paraoksonaze 1 i podložnost aterogenezi",
volume = "141",
number = "9-10",
pages = "629-633",
doi = "10.2298/SARH1310629G"
}
Grubiša, I., Otašević, P., Dimković, N., Nedeljković, I., Toljić, B.,& Vučinić, N.. (2013). Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 141(9-10), 629-633.
https://doi.org/10.2298/SARH1310629G
Grubiša I, Otašević P, Dimković N, Nedeljković I, Toljić B, Vučinić N. Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis. in Srpski arhiv za celokupno lekarstvo. 2013;141(9-10):629-633.
doi:10.2298/SARH1310629G .
Grubiša, Ivana, Otašević, Petar, Dimković, Nada, Nedeljković, Ivana, Toljić, Boško, Vučinić, Nada, "Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis" in Srpski arhiv za celokupno lekarstvo, 141, no. 9-10 (2013):629-633,
https://doi.org/10.2298/SARH1310629G . .

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