AbstractPurpose of review
With the completion of the human genome project and HapMap, previously unknown genetic polymorphisms associated with disease have been observed. This review highlights genetic polymorphisms that have provided insight into the pathophysiology underlying the many phenotypes of sickle cell disease.Recent findings
The phenotypes of sickle cell disease are likely to be modulated by polymorphisms in genes that are involved in inflammation, cell–cell interaction, and nitric oxide biology. Case–control studies are beginning to define the relationships between single-nucleotide polymorphisms in candidate genes and the many subphenotypes of sickle cell anemia. A common theme emerging from these studies is that single-nucleotide polymorphisms in genes of the transforming growth factor-β/bone morphogenetic protein and a few other genes such as Klotho are associated with several subphenotypes of sickle cell disease.Summary
Genomic medicine is merging with clinical practice as our understanding of the structure and variability of the human genome increases. Patients with diseases caused by identical mutations in a single gene – sickle cell anemia is a prime example – can have clinical courses very different from one another, and when environmental influences are removed the phenotypic heterogeneity of mendelian single-gene disorders is best explained by single-nucleotide polymorphisms in genes that modulate the disease phenotype. As this field expands, insights will be gained into complex epistatic factors that influence the clinical presentation of sickle cell disease, enabling physicians to better predict and manage the many complications of this disease.