Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy
Само за регистроване кориснике
2013
Аутори
Tafrali, ChristinaPaizi, 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.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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, a...s 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.
Кључне речи:
transcription profiling / sickle cell disease / pharmacogenomics / PDE7B / MAP3K5 / hydroxyurea / haplotype / beta-thalassemiaИзвор:
Pharmacogenomics, 2013, 14, 5, 469-483Издавач:
- Future Medicine Ltd, London
Финансирање / пројекти:
- long-term EMBO fellowship [ALTF 71-2011]
- Research Promotion Foundation of Cyprus grant [RPFPiLambdaE046_02]
- European Commission grant [FP7-200754]
- 'SEE-DRUG' project [FP7-REGPOT-2011-1]
DOI: 10.2217/PGS.13.31
ISSN: 1462-2416
PubMed: 23556445
WoS: 000317177700012
Scopus: 2-s2.0-84875936756
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .