TY  - JOUR
AU  - Srzentić Dražilov, Sanja
AU  - Nikčević, Gordana
AU  - Spasovski, Dusko
AU  - Bascarević, Zoran
AU  - Zivković, Zorica
AU  - Terzić-Supić, Zorica
AU  - Matanović, Dragana
AU  - Đorđević, Valentina
AU  - Pavlović, Sonja
AU  - Spasovski, Vesna
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/796
AB  - Perthes disease is one of the most common forms of pediatric femoral head osteonecrosis with an unknown etiology. Coagulation factors were the first genetic factors suspected to have a role in the pathogenesis of this disease, but studies showed inconsistent results. It is described that inflammation is present during early stages of Perthes disease, but its genetic aspect has not been studied extensively. Little is known regarding the status of apoptotic factors during the repair process that leads to the occurrence of hip deformity in patients. Therefore, the aim of this study was to analyze major mediators involved in coagulation, inflammation, and apoptotic processes as possible causative factors of Perthes disease. The study cohort consisted of 37 patients. Gene variants of TNF-alpha, FV, FII, and MTHFR genes were determined by PCR-RFLP, while IL-3 and PAI-1 were genotyped by direct sequencing. The expression level of Bax, Bcl-2, Bcl2L12, Fas and FasL was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) technique. Our results showed a significantly increased level of expression of pro-apoptotic factor Bax along with significantly higher Bax/Bcl-2 ratio in the patient group. Conclusion: The results presented indicate that apoptosis could be one of the factors contributing to the lack of balanced bone remodeling process in Perthes patients.
PB  - Springer, New York
T2  - European Journal of Pediatrics
T1  - Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease-Serbian experience
EP  - 1092
IS  - 8
SP  - 1085
VL  - 174
DO  - 10.1007/s00431-015-2510-z
ER  - 

@article{
author = "Srzentić Dražilov, Sanja and Nikčević, Gordana and Spasovski, Dusko and Bascarević, Zoran and Zivković, Zorica and Terzić-Supić, Zorica and Matanović, Dragana and Đorđević, Valentina and Pavlović, Sonja and Spasovski, Vesna",
year = "2015",
abstract = "Perthes disease is one of the most common forms of pediatric femoral head osteonecrosis with an unknown etiology. Coagulation factors were the first genetic factors suspected to have a role in the pathogenesis of this disease, but studies showed inconsistent results. It is described that inflammation is present during early stages of Perthes disease, but its genetic aspect has not been studied extensively. Little is known regarding the status of apoptotic factors during the repair process that leads to the occurrence of hip deformity in patients. Therefore, the aim of this study was to analyze major mediators involved in coagulation, inflammation, and apoptotic processes as possible causative factors of Perthes disease. The study cohort consisted of 37 patients. Gene variants of TNF-alpha, FV, FII, and MTHFR genes were determined by PCR-RFLP, while IL-3 and PAI-1 were genotyped by direct sequencing. The expression level of Bax, Bcl-2, Bcl2L12, Fas and FasL was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) technique. Our results showed a significantly increased level of expression of pro-apoptotic factor Bax along with significantly higher Bax/Bcl-2 ratio in the patient group. Conclusion: The results presented indicate that apoptosis could be one of the factors contributing to the lack of balanced bone remodeling process in Perthes patients.",
publisher = "Springer, New York",
journal = "European Journal of Pediatrics",
title = "Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease-Serbian experience",
pages = "1092-1085",
number = "8",
volume = "174",
doi = "10.1007/s00431-015-2510-z"
}

Srzentić Dražilov, S., Nikčević, G., Spasovski, D., Bascarević, Z., Zivković, Z., Terzić-Supić, Z., Matanović, D., Đorđević, V., Pavlović, S.,& Spasovski, V.. (2015). Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease-Serbian experience. in European Journal of Pediatrics
Springer, New York., 174(8), 1085-1092.
https://doi.org/10.1007/s00431-015-2510-z

Srzentić Dražilov S, Nikčević G, Spasovski D, Bascarević Z, Zivković Z, Terzić-Supić Z, Matanović D, Đorđević V, Pavlović S, Spasovski V. Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease-Serbian experience. in European Journal of Pediatrics. 2015;174(8):1085-1092.
doi:10.1007/s00431-015-2510-z .

Srzentić Dražilov, Sanja, Nikčević, Gordana, Spasovski, Dusko, Bascarević, Zoran, Zivković, Zorica, Terzić-Supić, Zorica, Matanović, Dragana, Đorđević, Valentina, Pavlović, Sonja, Spasovski, Vesna, "Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes disease-Serbian experience" in European Journal of Pediatrics, 174, no. 8 (2015):1085-1092,
https://doi.org/10.1007/s00431-015-2510-z . .

TY  - JOUR
AU  - Srzentić Dražilov, Sanja
AU  - Spasovski, Vesna
AU  - Spasovski, Duško
AU  - Živković, Zorica
AU  - Matanović, Dragana
AU  - Baščarević, Zoran
AU  - Šupić-Terzić, Zorica
AU  - Stojiljković, Maja
AU  - Karan-Đurašević, Teodora
AU  - Stanković, Biljana
AU  - Pavlović, Sonja
AU  - Nikčević, Gordana
AU  - Vukašinović, Zoran
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/752
AB  - Uvod Pertesova bolest je idiopatska avaskularna osteonekroza proksimalne epifize femura koja se javlja kod dece. Etiologija ove bolesti je nepoznata. Tokom razvoja Pertesove bolesti zastupljen je proces zapaljenja, za koji je pokazano da utiče na remodelovanje koštanog tkiva. Cilj rada S obzirom na to da genetički faktori koji utiču na proces zapaljenja dosad nisu ispitivani kod Pertesove bolesti, cilj ovog istraživanja je bio da se utvrdi povezanost učestalosti varijanti u genima koji učestvuju u inflamatornom odgovoru, TLR4 (engl. toll-like receptor 4) i IL-6 (interleukin 6), i ove bolesti. Metode rada Ispitano je 37 dece s Pertesovom bolešću i 50 zdravih osoba. Metodom PCR-RFLP određeni su polimorfizmi medijatora zapaljenja TLR4 (Asp299Gly, Thr399Ile) i IL-6 (G-174C, G-597A). Rezultati Pokazano je da su polimorfizmi IL-6 G-174C i G-597A u našem ispitivanju bili u potpunoj gametskoj neravnoteži vezanosti. U kontrolnoj grupi je bilo statistički značajno više nosilaca heterozigotnog genotipa IL-6 G-174C/G-597A u poređenju sa grupom ispitanika s Pertesovom bolešću (p=0,047; OR=2,49; 95% CI=1,00-6,21). Takođe, grupa bolesnika nije bila u Hardi- Vajnbergovoj ravnoteži za polimorfizme IL-6 G-174C/G-597A. Nije primećena statistički značajna razlika u raspodeli genotipova za polimorfizme analizirane u TLR4 genu. Raspodela genotipova među grupama bolesnika formiranih na osnovu uzrasta kada se bolest pojavila nije pokazala statistički značajnu povezanost s analiziranim polimorfizmima. Zaključak Naše istraživanje je pokazalo da su nosioci heterozigotnog genotipa za IL-6 G-174C/G-597A polimorfizme bili značajno češći u kontrolnoj grupi nego u grupi dece obolele od Pertesove bolesti. Na osnovu toga zaključili smo da je kod dece koja su nosioci heterozigotnog genotipa za ove polimorfizme manja verovatnoća za razvoj Pertesove bolesti nego kod nosilaca oba homozigotna genotipa.
AB  - Introduction Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling. Objective Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4) and interleukin-6 (IL-6), with this disease. Methods The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr399Ile) and IL-6 (G-174C, G- 597A) were determined by polymerase chain reaction restriction fragment length polymorphism method. Results IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p=0.047, OR=2.49, 95% CI=1.00-6.21). Also, the patient group for IL-6 G-174C/G- 597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću
T1  - Association of gene variants in TLR4 and IL-6 genes with Perthes disease
EP  - 456
IS  - 7-8
SP  - 450
VL  - 142
DO  - 10.2298/SARH1408450S
ER  - 

@article{
author = "Srzentić Dražilov, Sanja and Spasovski, Vesna and Spasovski, Duško and Živković, Zorica and Matanović, Dragana and Baščarević, Zoran and Šupić-Terzić, Zorica and Stojiljković, Maja and Karan-Đurašević, Teodora and Stanković, Biljana and Pavlović, Sonja and Nikčević, Gordana and Vukašinović, Zoran",
year = "2014",
abstract = "Uvod Pertesova bolest je idiopatska avaskularna osteonekroza proksimalne epifize femura koja se javlja kod dece. Etiologija ove bolesti je nepoznata. Tokom razvoja Pertesove bolesti zastupljen je proces zapaljenja, za koji je pokazano da utiče na remodelovanje koštanog tkiva. Cilj rada S obzirom na to da genetički faktori koji utiču na proces zapaljenja dosad nisu ispitivani kod Pertesove bolesti, cilj ovog istraživanja je bio da se utvrdi povezanost učestalosti varijanti u genima koji učestvuju u inflamatornom odgovoru, TLR4 (engl. toll-like receptor 4) i IL-6 (interleukin 6), i ove bolesti. Metode rada Ispitano je 37 dece s Pertesovom bolešću i 50 zdravih osoba. Metodom PCR-RFLP određeni su polimorfizmi medijatora zapaljenja TLR4 (Asp299Gly, Thr399Ile) i IL-6 (G-174C, G-597A). Rezultati Pokazano je da su polimorfizmi IL-6 G-174C i G-597A u našem ispitivanju bili u potpunoj gametskoj neravnoteži vezanosti. U kontrolnoj grupi je bilo statistički značajno više nosilaca heterozigotnog genotipa IL-6 G-174C/G-597A u poređenju sa grupom ispitanika s Pertesovom bolešću (p=0,047; OR=2,49; 95% CI=1,00-6,21). Takođe, grupa bolesnika nije bila u Hardi- Vajnbergovoj ravnoteži za polimorfizme IL-6 G-174C/G-597A. Nije primećena statistički značajna razlika u raspodeli genotipova za polimorfizme analizirane u TLR4 genu. Raspodela genotipova među grupama bolesnika formiranih na osnovu uzrasta kada se bolest pojavila nije pokazala statistički značajnu povezanost s analiziranim polimorfizmima. Zaključak Naše istraživanje je pokazalo da su nosioci heterozigotnog genotipa za IL-6 G-174C/G-597A polimorfizme bili značajno češći u kontrolnoj grupi nego u grupi dece obolele od Pertesove bolesti. Na osnovu toga zaključili smo da je kod dece koja su nosioci heterozigotnog genotipa za ove polimorfizme manja verovatnoća za razvoj Pertesove bolesti nego kod nosilaca oba homozigotna genotipa., Introduction Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling. Objective Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4) and interleukin-6 (IL-6), with this disease. Methods The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr399Ile) and IL-6 (G-174C, G- 597A) were determined by polymerase chain reaction restriction fragment length polymorphism method. Results IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p=0.047, OR=2.49, 95% CI=1.00-6.21). Also, the patient group for IL-6 G-174C/G- 597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću, Association of gene variants in TLR4 and IL-6 genes with Perthes disease",
pages = "456-450",
number = "7-8",
volume = "142",
doi = "10.2298/SARH1408450S"
}

Srzentić Dražilov, S., Spasovski, V., Spasovski, D., Živković, Z., Matanović, D., Baščarević, Z., Šupić-Terzić, Z., Stojiljković, M., Karan-Đurašević, T., Stanković, B., Pavlović, S., Nikčević, G.,& Vukašinović, Z.. (2014). Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 142(7-8), 450-456.
https://doi.org/10.2298/SARH1408450S

Srzentić Dražilov S, Spasovski V, Spasovski D, Živković Z, Matanović D, Baščarević Z, Šupić-Terzić Z, Stojiljković M, Karan-Đurašević T, Stanković B, Pavlović S, Nikčević G, Vukašinović Z. Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću. in Srpski arhiv za celokupno lekarstvo. 2014;142(7-8):450-456.
doi:10.2298/SARH1408450S .

Srzentić Dražilov, Sanja, Spasovski, Vesna, Spasovski, Duško, Živković, Zorica, Matanović, Dragana, Baščarević, Zoran, Šupić-Terzić, Zorica, Stojiljković, Maja, Karan-Đurašević, Teodora, Stanković, Biljana, Pavlović, Sonja, Nikčević, Gordana, Vukašinović, Zoran, "Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću" in Srpski arhiv za celokupno lekarstvo, 142, no. 7-8 (2014):450-456,
https://doi.org/10.2298/SARH1408450S . .