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 journalArticlepeer-review

10 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 languageEnglish
Pages (from-to)393-403
Number of pages11
JournalPharmacogenomics
Volume17
Issue number4
DOIs
Publication statusPublished - Mar 2016

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this