Genetic Etiologies for Phenotypic Diversity in Sickle Cell Anemia
Steinberg MH.
ScientificWorldJournal. 2009 Jan 18;9:46-67.


The clinical course of patients with sickle cell anemia, a Mendelian trait, is characteristically highly variable. HbF concentration and the presence of á 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-â/BMP 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.
Sickle-cell disease
Evolutionary ethics
'Artificial' evolution
Heterozygote advantage
Germline genetic engineering
Congenital insensitivity to pain
Human embryonic stem cell research
Gene therapy and performance enhancement
Human genetics of neurotransmitter transporters
Transhumanism (H+): toward a Brave New World?
Hematopoietic stem cell transplantation in sickle cell disease

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