Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia
Yıl: 2019 Cilt: 36 Sayı: 1 Sayfa Aralığı: 12 - 18 Metin Dili: İngilizce DOI: 10.4274/tjh.galenos.2018.2018.0221 İndeks Tarihi: 19-08-2020
Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia
Öz: Objective: In acute lymphoblastic leukemia (ALL), various clinical riskfactors and genetic predispositions contribute to the developmentof bone complications during and after chemotherapy. In this study,we aimed to investigate whether vitamin D receptor (VDR) Fok1 andcollagen protein Col1A1 Sp1-binding site gene polymorphisms, whichare important in bone mineral and matrix formation, have effects onthe development of bone abnormalities in childhood ALL survivors.Materials and Methods: Fifty children with ALL who were treated withthe ALL Berlin-Frankfurt-Muenster-95 protocol between 1998 and 2008and were followed for at least 7 years were enrolled. The control groupconsisted of 96 healthy children. VDR Fok1 and Col1A1 Sp1-bindingsite gene polymorphisms were analyzed by polymerase chain reactionand restriction fragment length polymorphism. Bone mineral density(BMD) and markers of bone metabolism were all noted. All patients whopresented with pain in the joints were examined for bone pathologieswhile on chemotherapy or during long-term follow-up.Results: Low BMD (16%), osteoporosis (12%), and osteonecrosis(8%) were present in a total of 18 patients (36%). The frequency ofosteonecrosis and total bone abnormalities was significantly higherin children aged ≥10 years (p=0.001). The risk of low BMD andosteonecrosis was higher in those with vitamin D deficiency. Only theCol1A1 Sp1-binding site gene polymorphism showed a significantassociation in ALL patients with osteonecrosis.Conclusion: The development of therapy-induced bone mineralloss and osteonecrosis in children with ALL is frequent and the riskis especially higher in children aged ≥10 years and with vitamin Ddeficiency. The association between Col1A1 Sp1-binding site genepolymorphisms and osteonecrosis has to be assessed in a larger groupof ALL survivors.
Anahtar Kelime: Akut Lenfoblastik Lösemili Çocuklarda Fok1 ve Col1A1 Gen Polimorfizmleri ile Tedaviye Bağlı Kemik Komplikasyonlarının Gelişimi Arasındaki İlişkinin Araştırılması
Öz: Amaç: Akut lenfoblastik lösemide (ALL), çeşitli klinik risk faktörleri ve genetik yatkınlıklar kemoterapi sırasında ve sonrasında kemik komplikasyonlarının gelişmesine katkıda bulunur. Bu çalışmada, kemik mineral ve matriks oluşumunda önemli olan D vitamini reseptörü (VDR) Fok1 ve kollajen proteini Col1A1 Sp1 bağlayıcı bölge gen polimorfizmlerinin, ALL’den sağ kalan çocuklarda kemik anormalliklerinin gelişimine etkilerinin olup olmadığını araştırmayı amaçladık. Gereç ve Yöntemler: 1998-2008 yılları arasında ALL tanısı alıp, ALL Berlin-Frankfurt-Muenster-95 protokolü ile tedavi edilen ve en az 7 yıl takip edilen 50 çocuk çalışmaya dahil edildi. Kontrol grubu 96 sağlıklı çocuktan oluşuyordu. VDR Fok1 ve Col1A1 Sp1 bağlayıcı bölge gen polimorfizmleri polimeraz zincir reaksiyonu ve restriksiyon fragman uzunluğu polimorfizmi ile analiz edildi. Kemik mineral yoğunluğu (KMY) ve kemik metabolizması belirteçleri kaydedildi. Eklemlerde ağrı ile başvuran tüm hastalar kemoterapi veya uzun süreli takip sırasında kemik patolojileri açısından incelendi. Bulgular: Toplam 18 hastada (%36) düşük KMY (%16), osteoporoz (%12) ve osteonekroz (%8) mevcuttu. Osteonekroz sıklığı ve toplam kemik anormallikleri 10 yaş ve üstü çocuklarda anlamlı olarak yüksek bulundu (p=0,001). D vitamini eksikliği olanlarda düşük BMD ve osteonekroz riski daha yüksekti. Gen polimorfizmleri ile ilişki incelendiğinde; sadece Col1A1 Sp1 bağlayıcı bölge gen polimorfizmi ile osteonekroz arasında anlamlı bir ilişki gösterilmiştir. Sonuç: Sonuç olarak, ALL’den sağ kalan çocuklarda tedaviye bağlı kemik mineral kaybı ve osteonekroz gelişimi sıktır ve bu risk özellikle 10 yaş ve üstü D vitamini eksikliği olan çocuklarda daha yüksektir. Col1A1 Sp1 bağlanma bölgesi gen polimorfizmleri ve osteonekroz arasındaki ilişkiyi araştırmak için ALL’den sağ kalan bireyler üzerinde yapılacak daha geniş çaplı çalışmalara ihtiyaç vardır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | ERDEM M, Tüfekçi Ö, KIZILDAG S, Yilmaz S, Kizmazoglu D, Eroğlu Filibeli B, Ören H (2019). Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. , 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| Chicago | ERDEM MELEK,Tüfekçi Özlem,KIZILDAG SEFA,Yilmaz Sebnem,Kizmazoglu Deniz,Eroğlu Filibeli Berna,Ören Hale Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. (2019): 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| MLA | ERDEM MELEK,Tüfekçi Özlem,KIZILDAG SEFA,Yilmaz Sebnem,Kizmazoglu Deniz,Eroğlu Filibeli Berna,Ören Hale Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. , 2019, ss.12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| AMA | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. . 2019; 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| Vancouver | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. . 2019; 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| IEEE | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H "Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia." , ss.12 - 18, 2019. 10.4274/tjh.galenos.2018.2018.0221 |
| ISNAD | ERDEM, MELEK vd. "Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia". (2019), 12-18. https://doi.org/10.4274/tjh.galenos.2018.2018.0221 |
| APA | ERDEM M, Tüfekçi Ö, KIZILDAG S, Yilmaz S, Kizmazoglu D, Eroğlu Filibeli B, Ören H (2019). Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. Turkish Journal of Hematology, 36(1), 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| Chicago | ERDEM MELEK,Tüfekçi Özlem,KIZILDAG SEFA,Yilmaz Sebnem,Kizmazoglu Deniz,Eroğlu Filibeli Berna,Ören Hale Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. Turkish Journal of Hematology 36, no.1 (2019): 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| MLA | ERDEM MELEK,Tüfekçi Özlem,KIZILDAG SEFA,Yilmaz Sebnem,Kizmazoglu Deniz,Eroğlu Filibeli Berna,Ören Hale Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. Turkish Journal of Hematology, vol.36, no.1, 2019, ss.12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| AMA | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. Turkish Journal of Hematology. 2019; 36(1): 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| Vancouver | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia. Turkish Journal of Hematology. 2019; 36(1): 12 - 18. 10.4274/tjh.galenos.2018.2018.0221 |
| IEEE | ERDEM M,Tüfekçi Ö,KIZILDAG S,Yilmaz S,Kizmazoglu D,Eroğlu Filibeli B,Ören H "Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia." Turkish Journal of Hematology, 36, ss.12 - 18, 2019. 10.4274/tjh.galenos.2018.2018.0221 |
| ISNAD | ERDEM, MELEK vd. "Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia". Turkish Journal of Hematology 36/1 (2019), 12-18. https://doi.org/10.4274/tjh.galenos.2018.2018.0221 |
