Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients

Constantina Chalikiopoulou; Anastasia Gerasimoula Tavianatou; Argyro Sgourou; Alexandra Kourakli; Dimitra Kelepouri; Maria Chrysanthakopoulou; Vasiliki Kaliopi Kanelaki; Evangelos Mourdoukoutas; Stavroula Siamoglou; Anne John; Argyris Symeonidis; Bassam R. Ali; Theodora Katsila; Adamantia Papachatzopoulou; George P. Patrinos

doi:10.2217/pgs.16.1

Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients

Constantina Chalikiopoulou, Anastasia Gerasimoula Tavianatou, Argyro Sgourou, Alexandra Kourakli, Dimitra Kelepouri, Maria Chrysanthakopoulou, Vasiliki Kaliopi Kanelaki, Evangelos Mourdoukoutas, Stavroula Siamoglou, Anne John, Argyris Symeonidis, Bassam R. Ali, Theodora Katsila, Adamantia Papachatzopoulou, George P. Patrinos

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

Aim: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Patients & methods: Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. Results: We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. Conclusion: These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.

Original language	English
Pages (from-to)	393-403
Number of pages	11
Journal	Pharmacogenomics
Volume	17
Issue number	4
DOIs	https://doi.org/10.2217/pgs.16.1
Publication status	Published - Mar 2016

Keywords

ASS1
NOS1
NOS2A
cGMP signaling
haplotype
hydroxyurea
nitric oxide
pharmacogenomics
β-thalassemia

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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Chalikiopoulou, C., Tavianatou, A. G., Sgourou, A., Kourakli, A., Kelepouri, D., Chrysanthakopoulou, M., Kanelaki, V. K., Mourdoukoutas, E., Siamoglou, S., John, A., Symeonidis, A., Ali, B. R., Katsila, T., Papachatzopoulou, A., & Patrinos, G. P. (2016). Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients. Pharmacogenomics, 17(4), 393-403. https://doi.org/10.2217/pgs.16.1

Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients. / Chalikiopoulou, Constantina; Tavianatou, Anastasia Gerasimoula; Sgourou, Argyro et al.
In: Pharmacogenomics, Vol. 17, No. 4, 03.2016, p. 393-403.

Research output: Contribution to journal › Article › peer-review

Chalikiopoulou, C, Tavianatou, AG, Sgourou, A, Kourakli, A, Kelepouri, D, Chrysanthakopoulou, M, Kanelaki, VK, Mourdoukoutas, E, Siamoglou, S, John, A, Symeonidis, A, Ali, BR, Katsila, T, Papachatzopoulou, A & Patrinos, GP 2016, 'Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients', Pharmacogenomics, vol. 17, no. 4, pp. 393-403. https://doi.org/10.2217/pgs.16.1

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abstract = "Aim: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Patients & methods: Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. Results: We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. Conclusion: These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.",

keywords = "ASS1, NOS1, NOS2A, cGMP signaling, haplotype, hydroxyurea, nitric oxide, pharmacogenomics, β-thalassemia",

author = "Constantina Chalikiopoulou and Tavianatou, {Anastasia Gerasimoula} and Argyro Sgourou and Alexandra Kourakli and Dimitra Kelepouri and Maria Chrysanthakopoulou and Kanelaki, {Vasiliki Kaliopi} and Evangelos Mourdoukoutas and Stavroula Siamoglou and Anne John and Argyris Symeonidis and Ali, {Bassam R.} and Theodora Katsila and Adamantia Papachatzopoulou and Patrinos, {George P.}",

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year = "2016",

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doi = "10.2217/pgs.16.1",

language = "English",

volume = "17",

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AU - Chalikiopoulou, Constantina

AU - Tavianatou, Anastasia Gerasimoula

AU - Sgourou, Argyro

AU - Kourakli, Alexandra

AU - Kelepouri, Dimitra

AU - Chrysanthakopoulou, Maria

AU - Kanelaki, Vasiliki Kaliopi

AU - Mourdoukoutas, Evangelos

AU - Siamoglou, Stavroula

AU - John, Anne

AU - Symeonidis, Argyris

AU - Ali, Bassam R.

AU - Katsila, Theodora

AU - Papachatzopoulou, Adamantia

AU - Patrinos, George P.

PY - 2016/3

Y1 - 2016/3

N2 - Aim: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Patients & methods: Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. Results: We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. Conclusion: These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.

AB - Aim: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Patients & methods: Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. Results: We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. Conclusion: These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.

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Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients

Abstract

Keywords

ASJC Scopus subject areas

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