The Scientific World Journal

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Review Article | Open Access

Volume 9 |Article ID 530852 |

Martin H. Steinberg, "Genetic Etiologies for Phenotypic Diversity in Sickle Cell Anemia", The Scientific World Journal, vol. 9, Article ID 530852, 22 pages, 2009.

Genetic Etiologies for Phenotypic Diversity in Sickle Cell Anemia

Academic Editor: Susan Perrine
Received07 Aug 2008
Revised19 Dec 2008
Accepted06 Jan 2009


The clinical course of patients with sickle cell anemia, a Mendelian trait, is characteristically highly variable. HbF concentration and the presence of a thalassemia are established modulators of the disease, but cannot account for all of its clinical heterogeneity. To find additional genetic modulators of disease, genotype-phenotype association studies, where single nucleotide polymorphisms (SNPs) in candidate genes are linked with a particular phenotype, have been informative. SNPs in several genes of the TGF-ß/MP superfamily, and some other genes linked to the endothelial function, and nitric oxide biology are associated with the subphenotypes of stroke, osteonecrosis, priapism, leg ulcers, pulmonary hypertension, and a more general measure of overall disease severity. Genome-wide association studies should help to confirm these observations and also to find hitherto unsuspected genetic modulators. Genetic association studies can have immediate prognostic value; they might also help to identify new pathophysiological pathways that could be susceptible to modulation.

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