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
Pharmacogenomics 17(4):393-403, February 2016
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.
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.
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.