TY  - JOUR
AU  - Stanković, Marija
AU  - Đorđević, Valentina
AU  - Tomović, Valentina
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1654
AB  - Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (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 interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments.
AB  - Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti 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 otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.
PB  - Belgrade : Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease
T1  - Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća
EP  - 104
IS  - 1
SP  - 94
VL  - 41
DO  - 10.5937/jomb0-34017
ER  - 

@article{
author = "Stanković, Marija and Đorđević, Valentina and Tomović, Valentina and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Kovač, Mirjana and Radojković, Dragica",
year = "2023",
abstract = "Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (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 interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments., Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti 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 otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.",
publisher = "Belgrade : Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease, Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća",
pages = "104-94",
number = "1",
volume = "41",
doi = "10.5937/jomb0-34017"
}

Stanković, M., Đorđević, V., Tomović, V., Nagorni-Obradović, L., Petrović-Stanojević, N., Kovač, M.,& Radojković, D.. (2023). Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry
Belgrade : Society of Medical Biochemists of Serbia., 41(1), 94-104.
https://doi.org/10.5937/jomb0-34017

Stanković M, Đorđević V, Tomović V, Nagorni-Obradović L, Petrović-Stanojević N, Kovač M, Radojković D. Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry. 2023;41(1):94-104.
doi:10.5937/jomb0-34017 .

Stanković, Marija, Đorđević, Valentina, Tomović, Valentina, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Kovač, Mirjana, Radojković, Dragica, "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease" in Journal of Medical Biochemistry, 41, no. 1 (2023):94-104,
https://doi.org/10.5937/jomb0-34017 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Mirković, Duško
AU  - Dudvarski-Llić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Đorđević, Valentina
AU  - Ignjatović, Svetlana
AU  - Majkić-Singh, Nada
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/839
AB  - Uvod: Povišena koncentracija homocisteina (Hey) može predstavljati metabolički marker nedostatka folata i vitamina B12, značajnih problema javnog zdravlja. Bolesnici sa hroničnom opstruktivnom bolešću pluća (HOBP) skloni su nedostatku ovih vitamina usled različitih razloga. Prikazana studija procenjuje pouzdanost koncentracije Hcy kao prediktora nedostatka folata i vitamina B12 kod ovih bolesnika. Metode: Studija je sprovedena u grupi od 50 osoba obolelih od HOBP (28 muškaraca/22 žene, starosti (x±SD = 49,0±14,5) godina. Koncentracije Hcy, folata i vitamina B12 su određivane hemiluminiscentnim imunoodređivanjem na mikročesticama. Statistička analiza je uključila testove Kolmogorov-Smirnov, Mann-Whitney U and x2, Spearman-ovu korelaciju i ROC analizu, uz nivo značajnosti od 0,05. Rezultati: Prosečne (SD) koncentracije folata i vitamina B-12 su iznosile 4,15 (2,16) pg/L i 465,6 (271,0) ng/L, pri čemu je samo kod vitamina B12 uočena korelacija sa nivoom Hcy (R =-0,510 (P=0,029)). Koncentracije vitamina se nisu razlikovale između polova, a starost je bila u korelaciji samo sa nivoom folata (R= 0,279 (P=0,047)). Incidenca nedostatka vitamina značajno se razlikovala (P=0,000 i P lt 0,000 za folat odn. vitamin B12) u zavisnosti od cut-off vrednosti u odnosu na koju je definisana (4,4; 6,6 i 8,0 pg/L - folat; 203 i 473 ng/L - vitamin B-12)-ROC analizom nije bilo moguće dokazati značaj hiperhomocisteinemije kao prediktora deficijencije. Zaključak: Pouzdanost koncentracije Hey kao markera nedostatka folata ili vitamina B12 kod bolesnika sa HOBP nije zadovoljavajuća, pa se deficijencija ovih vitamina ne može predvideti na osnovu pojave hiperhomocisteinemije.
AB  - Background: An increased homocysteine (Hey) concentration may represent a metabolic marker of folate and vitamin Bi2 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hey concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x±S D = 49.0±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and x2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.15 (2.16) pg/L and 465.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hey level (P =-0.510 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R = 0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and PcO.OOO for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 pg/L - folate; 203 and 473 ng/L - vitamin B12)-ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hey concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Neizvesna pouzdanost homocisteina kao metaboličkog markera za nedostatak folata i vitamina B12 kod pacijenata sa hroničnom opstruktivnom bolešću pluća
T1  - Questionable reliability of homocysteine as the metabolic marker for folate and vitamin B12 deficiency in patients with chronic obstructive pulmonary disease
EP  - 472
IS  - 4
SP  - 467
VL  - 34
DO  - 10.2478/jomb-2014-0046
ER  - 

@article{
author = "Beletić, Anđelo and Mirković, Duško and Dudvarski-Llić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Đorđević, Valentina and Ignjatović, Svetlana and Majkić-Singh, Nada",
year = "2015",
abstract = "Uvod: Povišena koncentracija homocisteina (Hey) može predstavljati metabolički marker nedostatka folata i vitamina B12, značajnih problema javnog zdravlja. Bolesnici sa hroničnom opstruktivnom bolešću pluća (HOBP) skloni su nedostatku ovih vitamina usled različitih razloga. Prikazana studija procenjuje pouzdanost koncentracije Hcy kao prediktora nedostatka folata i vitamina B12 kod ovih bolesnika. Metode: Studija je sprovedena u grupi od 50 osoba obolelih od HOBP (28 muškaraca/22 žene, starosti (x±SD = 49,0±14,5) godina. Koncentracije Hcy, folata i vitamina B12 su određivane hemiluminiscentnim imunoodređivanjem na mikročesticama. Statistička analiza je uključila testove Kolmogorov-Smirnov, Mann-Whitney U and x2, Spearman-ovu korelaciju i ROC analizu, uz nivo značajnosti od 0,05. Rezultati: Prosečne (SD) koncentracije folata i vitamina B-12 su iznosile 4,15 (2,16) pg/L i 465,6 (271,0) ng/L, pri čemu je samo kod vitamina B12 uočena korelacija sa nivoom Hcy (R =-0,510 (P=0,029)). Koncentracije vitamina se nisu razlikovale između polova, a starost je bila u korelaciji samo sa nivoom folata (R= 0,279 (P=0,047)). Incidenca nedostatka vitamina značajno se razlikovala (P=0,000 i P lt 0,000 za folat odn. vitamin B12) u zavisnosti od cut-off vrednosti u odnosu na koju je definisana (4,4; 6,6 i 8,0 pg/L - folat; 203 i 473 ng/L - vitamin B-12)-ROC analizom nije bilo moguće dokazati značaj hiperhomocisteinemije kao prediktora deficijencije. Zaključak: Pouzdanost koncentracije Hey kao markera nedostatka folata ili vitamina B12 kod bolesnika sa HOBP nije zadovoljavajuća, pa se deficijencija ovih vitamina ne može predvideti na osnovu pojave hiperhomocisteinemije., Background: An increased homocysteine (Hey) concentration may represent a metabolic marker of folate and vitamin Bi2 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hey concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x±S D = 49.0±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and x2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.15 (2.16) pg/L and 465.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hey level (P =-0.510 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R = 0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and PcO.OOO for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 pg/L - folate; 203 and 473 ng/L - vitamin B12)-ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hey concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Neizvesna pouzdanost homocisteina kao metaboličkog markera za nedostatak folata i vitamina B12 kod pacijenata sa hroničnom opstruktivnom bolešću pluća, Questionable reliability of homocysteine as the metabolic marker for folate and vitamin B12 deficiency in patients with chronic obstructive pulmonary disease",
pages = "472-467",
number = "4",
volume = "34",
doi = "10.2478/jomb-2014-0046"
}

Beletić, A., Mirković, D., Dudvarski-Llić, A., Milenković, B., Nagorni-Obradović, L., Đorđević, V., Ignjatović, S.,& Majkić-Singh, N.. (2015). Neizvesna pouzdanost homocisteina kao metaboličkog markera za nedostatak folata i vitamina B12 kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(4), 467-472.
https://doi.org/10.2478/jomb-2014-0046

Beletić A, Mirković D, Dudvarski-Llić A, Milenković B, Nagorni-Obradović L, Đorđević V, Ignjatović S, Majkić-Singh N. Neizvesna pouzdanost homocisteina kao metaboličkog markera za nedostatak folata i vitamina B12 kod pacijenata sa hroničnom opstruktivnom bolešću pluća. in Journal of Medical Biochemistry. 2015;34(4):467-472.
doi:10.2478/jomb-2014-0046 .

Beletić, Anđelo, Mirković, Duško, Dudvarski-Llić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Đorđević, Valentina, Ignjatović, Svetlana, Majkić-Singh, Nada, "Neizvesna pouzdanost homocisteina kao metaboličkog markera za nedostatak folata i vitamina B12 kod pacijenata sa hroničnom opstruktivnom bolešću pluća" in Journal of Medical Biochemistry, 34, no. 4 (2015):467-472,
https://doi.org/10.2478/jomb-2014-0046 . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Tomović, Andrija
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Radojković, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/849
AB  - 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 ispitivanje 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 113H is/(H is) (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.
AB  - 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 l2 2 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A /*2A , CYP2E1 *1 A /*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.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji
T1  - Association of functional variants of phase I and II genes with chronic obstructive pulmonary disease in a Serbian population
EP  - 214
IS  - 2
SP  - 207
VL  - 34
DO  - 10.2478/jomb-2014-0024
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Tomović, Andrija and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Radojković, Dragica",
year = "2015",
abstract = "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 ispitivanje 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 113H is/(H is) (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., 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 l2 2 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A /*2A , CYP2E1 *1 A /*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.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji, Association of functional variants of phase I and II genes with chronic obstructive pulmonary disease in a Serbian population",
pages = "214-207",
number = "2",
volume = "34",
doi = "10.2478/jomb-2014-0024"
}

Stanković, M., Nikolić, A., Tomović, A., Mitić-Milikić, M., Nagorni-Obradović, L., Petrović-Stanojević, N.,& Radojković, D.. (2015). Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(2), 207-214.
https://doi.org/10.2478/jomb-2014-0024

Stanković M, Nikolić A, Tomović A, Mitić-Milikić M, Nagorni-Obradović L, Petrović-Stanojević N, Radojković D. Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji. in Journal of Medical Biochemistry. 2015;34(2):207-214.
doi:10.2478/jomb-2014-0024 .

Stanković, Marija, Nikolić, Aleksandra, Tomović, Andrija, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Radojković, Dragica, "Udruženost funkcionalnih varijanti gena faze I I II sa hroničnom opstruktivnom bolešću pluća u srpskoj populaciji" in Journal of Medical Biochemistry, 34, no. 2 (2015):207-214,
https://doi.org/10.2478/jomb-2014-0024 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Ljujić, Mila
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
AU  - Majkić-Singh, Nada
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/767
AB  - Primarna uloga alfa-1-antitripsina (AAT) jeste da zaštiti plućni parenhim od proteolize dejstvom neutrofilne elastaze. Njegovu biosintezu kontroliše izuzetno polimorfni GEN SERPINA1. Deficijencija AAT (AATD) jeste autozomalno recesivno oboljenje i smatra se najčešćim genetskim uzrokom oboljenja jetre kod dece i emfizema kod odraslih. Prema učestalosti, deficijentni aleli se mogu podeliti na "česte" (Z i S) i "retke" (Mmalton, Mheerlen, Mprocida itd.). Za vrstu, intenzitet i vremenski period u kome se razvijaju kliničke manifestacije smatra se odgovornim interakcija AATD i dodatnih genetskih i stečenih faktora rizika (pušenje, izloženost aerozagađenju i sl.). Kod obolelih se najčešće javljaju preuranjen emfizem, hronični hepatitis, ciroza i hepatocelularni karcinom. Epidemiološke studije naglašavaju potrebu povećanja dijagnostičke efikasnosti kod AATD. Preporučuje se da dijagnostički pristup integriše precizne, međunarodno identifikovane, kliničke kriterijume i standardizovan laboratorijski protokol, zasnovan na biohemijskim i molekularno-biološkim metodama. Terapijski pristup zavisi od vrste kliničkih manifestacija. Kod pulmoloških bolesnika je moguće primeniti terapiju nadoknade, dok kod osoba sa terminalnom fazom oštećenja jetre uzrokovanog AATD transplantacija trenutno predstavlja jedinu specifičnu terapiju. Kod svih obolelih je neophodno preventivno uticati na smanjenje štetnog uticaja životnih navika i faktora sredine. Očekuje se da zdravstveni ishodi kod obolelih budu značajno unapređeni uvođenjem genske terapije. Dosadašnji rezultati istraživanja efikasnosti integrativnog pristupa detekciji AATD u populaciji Srbije su ohrabrujući i upućuju na potrebu njegovog omasovljenja, čime bi se ostvarili uslovi za formiranje nacionalnog registra obolelih.
AB  - The primary role of Alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as "common" (Z and S) and "rare" (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Deficijencija alfa-1-antitripsina - molekulske osnove, kliničke manifestacije, terapijske mogućnosti i integrativni pristup u dijagnostici
T1  - Alpha-1-antitrypsin deficiency: Molecular basis, clinical presentation, therapeutic options and an integrative approach in diagnostics
EP  - 96
IS  - 1
SP  - 88
VL  - 33
DO  - 10.2478/jomb-2013-0038
ER  - 

@article{
author = "Beletić, Anđelo and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Ljujić, Mila and Đorđević, Valentina and Radojković, Dragica and Majkić-Singh, Nada",
year = "2014",
abstract = "Primarna uloga alfa-1-antitripsina (AAT) jeste da zaštiti plućni parenhim od proteolize dejstvom neutrofilne elastaze. Njegovu biosintezu kontroliše izuzetno polimorfni GEN SERPINA1. Deficijencija AAT (AATD) jeste autozomalno recesivno oboljenje i smatra se najčešćim genetskim uzrokom oboljenja jetre kod dece i emfizema kod odraslih. Prema učestalosti, deficijentni aleli se mogu podeliti na "česte" (Z i S) i "retke" (Mmalton, Mheerlen, Mprocida itd.). Za vrstu, intenzitet i vremenski period u kome se razvijaju kliničke manifestacije smatra se odgovornim interakcija AATD i dodatnih genetskih i stečenih faktora rizika (pušenje, izloženost aerozagađenju i sl.). Kod obolelih se najčešće javljaju preuranjen emfizem, hronični hepatitis, ciroza i hepatocelularni karcinom. Epidemiološke studije naglašavaju potrebu povećanja dijagnostičke efikasnosti kod AATD. Preporučuje se da dijagnostički pristup integriše precizne, međunarodno identifikovane, kliničke kriterijume i standardizovan laboratorijski protokol, zasnovan na biohemijskim i molekularno-biološkim metodama. Terapijski pristup zavisi od vrste kliničkih manifestacija. Kod pulmoloških bolesnika je moguće primeniti terapiju nadoknade, dok kod osoba sa terminalnom fazom oštećenja jetre uzrokovanog AATD transplantacija trenutno predstavlja jedinu specifičnu terapiju. Kod svih obolelih je neophodno preventivno uticati na smanjenje štetnog uticaja životnih navika i faktora sredine. Očekuje se da zdravstveni ishodi kod obolelih budu značajno unapređeni uvođenjem genske terapije. Dosadašnji rezultati istraživanja efikasnosti integrativnog pristupa detekciji AATD u populaciji Srbije su ohrabrujući i upućuju na potrebu njegovog omasovljenja, čime bi se ostvarili uslovi za formiranje nacionalnog registra obolelih., The primary role of Alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as "common" (Z and S) and "rare" (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Deficijencija alfa-1-antitripsina - molekulske osnove, kliničke manifestacije, terapijske mogućnosti i integrativni pristup u dijagnostici, Alpha-1-antitrypsin deficiency: Molecular basis, clinical presentation, therapeutic options and an integrative approach in diagnostics",
pages = "96-88",
number = "1",
volume = "33",
doi = "10.2478/jomb-2013-0038"
}

Beletić, A., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Ljujić, M., Đorđević, V., Radojković, D.,& Majkić-Singh, N.. (2014). Deficijencija alfa-1-antitripsina - molekulske osnove, kliničke manifestacije, terapijske mogućnosti i integrativni pristup u dijagnostici. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 33(1), 88-96.
https://doi.org/10.2478/jomb-2013-0038

Beletić A, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Ljujić M, Đorđević V, Radojković D, Majkić-Singh N. Deficijencija alfa-1-antitripsina - molekulske osnove, kliničke manifestacije, terapijske mogućnosti i integrativni pristup u dijagnostici. in Journal of Medical Biochemistry. 2014;33(1):88-96.
doi:10.2478/jomb-2013-0038 .

Beletić, Anđelo, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Ljujić, Mila, Đorđević, Valentina, Radojković, Dragica, Majkić-Singh, Nada, "Deficijencija alfa-1-antitripsina - molekulske osnove, kliničke manifestacije, terapijske mogućnosti i integrativni pristup u dijagnostici" in Journal of Medical Biochemistry, 33, no. 1 (2014):88-96,
https://doi.org/10.2478/jomb-2013-0038 . .