Sickle cell disease: A multigenic perspective of a single-gene disorder

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9 Scopus citations


Although significant progress has been made in our understanding of sickle cell disease (SCD) and in the development of new therapies, many questions are still unanswered, and a cure remains elusive. This is particularly evident in the clinical heterogeneity of the disease. Studies have shown the importance of high hemoglobin F determinants and α-thalassemia as modifiers of disease severity, but these alone do not explain the diversity that is seen. This paper focuses on recent advances on the effect of nonglobin genetic modifiers on the SCD phenotype. The roles of polymorphic variants of (1) methylene- tetrahydrofolate reductase gene in the pathogenesis of avascular necrosis, (2) factor V R485Kand risk of venous thrombosis, and (3) UDP glucuronosyltransferase-1 polymorphism on serum bilirubin levels in SCD are discussed. Mention is made of genetic polymorphisms that might predispose to stroke. The application of gene expression profiling to the study of SCD is very promising and some preliminary data are provided.

Original languageEnglish (US)
Pages (from-to)15-19
Number of pages5
JournalMedical Principles and Practice
Issue numberSUPPL. 1
StatePublished - Aug 26 2005


  • Genetic polymorphisms
  • Sickle cell disease

ASJC Scopus subject areas

  • Medicine(all)


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