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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.
- Source :
-
Pharmacogenomics [Pharmacogenomics] 2016 Mar; Vol. 17 (4), pp. 393-403. Date of Electronic Publication: 2016 Feb 19. - Publication Year :
- 2016
-
Abstract
- Aim: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes.<br />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.<br />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.<br />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.
- Subjects :
- Anemia, Sickle Cell complications
Anemia, Sickle Cell drug therapy
Case-Control Studies
Genetic Variation
Humans
Nitric Oxide genetics
Nitric Oxide Synthase Type I genetics
Nitric Oxide Synthase Type II genetics
beta-Thalassemia complications
beta-Thalassemia drug therapy
Anemia, Sickle Cell genetics
Antisickling Agents therapeutic use
Argininosuccinate Synthase genetics
Hydroxyurea therapeutic use
Nitric Oxide biosynthesis
beta-Thalassemia genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8042
- Volume :
- 17
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Pharmacogenomics
- Publication Type :
- Academic Journal
- Accession number :
- 26895070
- Full Text :
- https://doi.org/10.2217/pgs.16.1