Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment

Expert Rev Hematol. 2010 Aug;3(4):443-58. doi: 10.1586/ehm.10.44.


Sickle cell disease (SCD) is one of the best characterized human monogenic disorders. The development of molecular biology allowed the identification of several genomic polymorphisms responsible for its clinical diversity. Research on the first genetic modulators of SCD, such as coinheritance of α-thalassemia and haplotypes in the β-globin gene cluster, have been followed by studies associating single nucleotide polymorphisms (SNPs) with variable risks for stroke, leg ulceration, pulmonary hypertension, priapism and osteonecrosis, with differences in the response to hydroxyurea, and with variability in the management of pain. Furthermore, multigenic analyses based on genome-wide association studies have shed light on the importance of the TGF-β superfamily and oxidative stress to the pathogenesis of complex traits in SCD, and may guide future therapeutic interventions on a genetically oriented basis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Sickle Cell / drug therapy
  • Anemia, Sickle Cell / genetics*
  • Anemia, Sickle Cell / pathology*
  • Anemia, Sickle Cell / therapy
  • Antisickling Agents / therapeutic use
  • Blood Transfusion
  • Fetal Hemoglobin / genetics
  • Genome-Wide Association Study
  • Humans
  • Hydroxyurea / therapeutic use
  • Male
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*


  • Antisickling Agents
  • Fetal Hemoglobin
  • Hydroxyurea