TY  - JOUR
AU  - Bačković, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Ćalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/988
AB  - Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija.
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije
T1  - Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis
EP  - 33
IS  - 1
SP  - 26
VL  - 35
DO  - 10.1515/jomb-2015-0009
ER  - 

@article{
author = "Bačković, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica and Ćalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovač, Mirjana",
year = "2016",
abstract = "Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija., Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije, Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis",
pages = "33-26",
number = "1",
volume = "35",
doi = "10.1515/jomb-2015-0009"
}

Bačković, D., Ignjatović, S., Rakićević, L., Kušić-Tišma, J., Radojković, D., Ćalija, B., Strugarević, E., Radak, Đ.,& Kovač, M.. (2016). Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009

Bačković D, Ignjatović S, Rakićević L, Kušić-Tišma J, Radojković D, Ćalija B, Strugarević E, Radak Đ, Kovač M. Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .

Bačković, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, Ćalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovač, Mirjana, "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Calija, Branko
AU  - Radak, Djordje
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/920
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
EP  - 569
IS  - 6
SP  - 563
VL  - 14
DO  - 10.2174/1570161114666160714103148
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Calija, Branko and Radak, Djordje and Kovač, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
pages = "569-563",
number = "6",
volume = "14",
doi = "10.2174/1570161114666160714103148"
}

Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148

Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .

Backović, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Calija, Branko, Radak, Djordje, Kovač, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .

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  - Beletić, Anđelo
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Ljujić, Mila
AU  - Đorđević, Valentina
AU  - Mirković, Dusko
AU  - Radojković, Dragica
AU  - Majkic-Singh, Nada
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/715
AB  - Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.
PB  - Croatian Soc Medical Biochemists, Zagreb
T2  - Biochemia Medica
T1  - Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
EP  - 298
IS  - 2
SP  - 293
VL  - 24
DO  - 10.11613/BM.2014.032
ER  - 

@article{
author = "Beletić, Anđelo and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Ljujić, Mila and Đorđević, Valentina and Mirković, Dusko and Radojković, Dragica and Majkic-Singh, Nada",
year = "2014",
abstract = "Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.",
publisher = "Croatian Soc Medical Biochemists, Zagreb",
journal = "Biochemia Medica",
title = "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?",
pages = "298-293",
number = "2",
volume = "24",
doi = "10.11613/BM.2014.032"
}

Beletić, A., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Ljujić, M., Đorđević, V., Mirković, D., Radojković, D.,& Majkic-Singh, N.. (2014). Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica
Croatian Soc Medical Biochemists, Zagreb., 24(2), 293-298.
https://doi.org/10.11613/BM.2014.032

Beletić A, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Ljujić M, Đorđević V, Mirković D, Radojković D, Majkic-Singh N. Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica. 2014;24(2):293-298.
doi:10.11613/BM.2014.032 .

Beletić, Anđelo, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Ljujić, Mila, Đorđević, Valentina, Mirković, Dusko, Radojković, Dragica, Majkic-Singh, Nada, "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?" in Biochemia Medica, 24, no. 2 (2014):293-298,
https://doi.org/10.11613/BM.2014.032 . .

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 . .