Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću
Association of gene variants in TLR4 and IL-6 genes with Perthes disease
2014
Authors
Srzentić Dražilov, SanjaSpasovski, 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
Article (Published version)
Metadata
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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 ge...notipa 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-5...97A 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.
Keywords:
Pertesova bolest / inflamacija / genske varijante / Perthes disease / inflammation / gene variantsSource:
Srpski arhiv za celokupno lekarstvo, 2014, 142, 7-8, 450-456Publisher:
- Srpsko lekarsko društvo, Beograd
Funding / projects:
- Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.2298/SARH1408450S
ISSN: 0370-8179
PubMed: 25233690
WoS: 000341069800008
Scopus: 2-s2.0-84922605039
Collections
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .