Genetic etiologies for phenotypic diversity in sickle cell anemia.
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-beta/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.
Steinberg
Martin H
MH
Boston University School of Medicine, Boston, MA 02118, USA. mhsteinb@bu.edu
D000755:Anemia, Sickle Cell / Q000097:blood / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017085:alpha-Thalassemia / Q000145:classification / Q000150:complications / Q000235:genetics / Q000378:metabolism
D005319:Fetal Hemoglobin