TY  - JOUR
AU  - Tafrali, Christina
AU  - Paizi, Arsinoi
AU  - Borg, Joseph
AU  - Radmilović Milena
AU  - Bartsakoulia, Marina
AU  - Giannopoulou, Emily
AU  - Giannakopoulou, Olga
AU  - Stojiljković, Maja
AU  - Zukić, Branka
AU  - Poulas, Konstantinos
AU  - Stavrou, Eleana F.
AU  - Lambropoulou, Polyxeni
AU  - Kourakli, Alexandra
AU  - Felice, Alexander E.
AU  - Papachatzopoulou, Adamantia
AU  - Philipsen, Sjaak
AU  - Pavlović, Sonja
AU  - Georgitsi, Marianthi
AU  - Patrinos, George P.
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/640
AB  - Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta-hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Materials & methods: For this purpose, we genotyped beta-thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease/beta-thalassemia patients receiving HU as HbF augmentation treatment. Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU. Lastly, the above-mentioned MAP3K5 variants are associated with HU treatment efficacy. Conclusion: Our data suggest that these MAP3K5 variants are indicative of b-thalassemia disease severity and response to HU treatment.
PB  - Future Medicine Ltd, London
T2  - Pharmacogenomics
T1  - Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy
EP  - 483
IS  - 5
SP  - 469
VL  - 14
DO  - 10.2217/PGS.13.31
ER  - 

@article{
author = "Tafrali, Christina and Paizi, Arsinoi and Borg, Joseph and Radmilović Milena and Bartsakoulia, Marina and Giannopoulou, Emily and Giannakopoulou, Olga and Stojiljković, Maja and Zukić, Branka and Poulas, Konstantinos and Stavrou, Eleana F. and Lambropoulou, Polyxeni and Kourakli, Alexandra and Felice, Alexander E. and Papachatzopoulou, Adamantia and Philipsen, Sjaak and Pavlović, Sonja and Georgitsi, Marianthi and Patrinos, George P.",
year = "2013",
abstract = "Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta-hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Materials & methods: For this purpose, we genotyped beta-thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease/beta-thalassemia patients receiving HU as HbF augmentation treatment. Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU. Lastly, the above-mentioned MAP3K5 variants are associated with HU treatment efficacy. Conclusion: Our data suggest that these MAP3K5 variants are indicative of b-thalassemia disease severity and response to HU treatment.",
publisher = "Future Medicine Ltd, London",
journal = "Pharmacogenomics",
title = "Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy",
pages = "483-469",
number = "5",
volume = "14",
doi = "10.2217/PGS.13.31"
}

Tafrali, C., Paizi, A., Borg, J., Radmilović Milena, Bartsakoulia, M., Giannopoulou, E., Giannakopoulou, O., Stojiljković, M., Zukić, B., Poulas, K., Stavrou, E. F., Lambropoulou, P., Kourakli, A., Felice, A. E., Papachatzopoulou, A., Philipsen, S., Pavlović, S., Georgitsi, M.,& Patrinos, G. P.. (2013). Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy. in Pharmacogenomics
Future Medicine Ltd, London., 14(5), 469-483.
https://doi.org/10.2217/PGS.13.31

Tafrali C, Paizi A, Borg J, Radmilović Milena, Bartsakoulia M, Giannopoulou E, Giannakopoulou O, Stojiljković M, Zukić B, Poulas K, Stavrou EF, Lambropoulou P, Kourakli A, Felice AE, Papachatzopoulou A, Philipsen S, Pavlović S, Georgitsi M, Patrinos GP. Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy. in Pharmacogenomics. 2013;14(5):469-483.
doi:10.2217/PGS.13.31 .

Tafrali, Christina, Paizi, Arsinoi, Borg, Joseph, Radmilović Milena, Bartsakoulia, Marina, Giannopoulou, Emily, Giannakopoulou, Olga, Stojiljković, Maja, Zukić, Branka, Poulas, Konstantinos, Stavrou, Eleana F., Lambropoulou, Polyxeni, Kourakli, Alexandra, Felice, Alexander E., Papachatzopoulou, Adamantia, Philipsen, Sjaak, Pavlović, Sonja, Georgitsi, Marianthi, Patrinos, George P., "Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy" in Pharmacogenomics, 14, no. 5 (2013):469-483,
https://doi.org/10.2217/PGS.13.31 . .