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Review
. 2012 Aug;87(8):795-803.
doi: 10.1002/ajh.23232. Epub 2012 May 28.

Genetic modifiers of sickle cell disease

Affiliations
Review

Genetic modifiers of sickle cell disease

Martin H Steinberg et al. Am J Hematol. 2012 Aug.

Abstract

Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident α thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new "druggable" pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease.

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Figures

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Genetic modifiers of sickle cell disease
Heritability of hemolytic score. The scatter plot in panel (A) shows hemolytic score of sib pairs (r = 0.24, p = 0.02) while panel (B) shows HbF of pairs of unrelated subjects (r = 0.001, p = 0.52). (C) Manhattan plot summarizing the results of GWAS of hemolytic score. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

References

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    1. Steinberg MH, Embury SH. Alpha-thalassemia in blacks: genetic and clinical aspects and interactions with the sickle hemoglobin gene. Blood. 1986;68:985–90. - PubMed
    1. Steinberg MH. Predicting clinical severity in sickle cell anaemia. Br J Haematol. 2005;129:465–81. - PubMed

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