TY - JOUR
T1 - 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
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.
N1 - Publisher Copyright:
© 2016 Future Medicine Ltd.
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.
KW - ASS1
KW - NOS1
KW - NOS2A
KW - cGMP signaling
KW - haplotype
KW - hydroxyurea
KW - nitric oxide
KW - pharmacogenomics
KW - β-thalassemia
UR - http://www.scopus.com/inward/record.url?scp=84960845917&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960845917&partnerID=8YFLogxK
U2 - 10.2217/pgs.16.1
DO - 10.2217/pgs.16.1
M3 - Article
C2 - 26895070
AN - SCOPUS:84960845917
SN - 1462-2416
VL - 17
SP - 393
EP - 403
JO - Pharmacogenomics
JF - Pharmacogenomics
IS - 4
ER -