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:

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.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

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

doi

10.2217/pgs.16.1

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

393-403

issue

4

eissn

1462-2416

issn

1744-8042

journal_volume

17

pub_type

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