title: Minireview: Genetic basis of heterogeneity and severity in sickle cell disease.
abstract: Sickle cell disease, a common single gene disorder, has a complex pathophysiology that at its root is initiated by the polymerization of deoxy sickle hemoglobin. Sickle vasoocclusion and hemolytic anemia drive the development of disease complications. In this review, we focus on the genetic modifiers of disease heterogeneity. The phenotypic heterogeneity of disease is only partially explained by genetic variability of fetal hemoglobin gene expression and co-inheritance of α thalassemia. Given the complexity of pathophysiology, many different definitions of severity are possible complicating a full understanding of its genetic foundation. The pathophysiological complexity and the interlocking nature of the biological processes underpinning disease severity are becoming better understood. Nevertheless, useful genetic signatures of severity, regardless of how this is defined, are insufficiently developed to be used for treatment decisions and for counseling.
authors.affiliation: Department of Clinical Biochemistry, College of Medicine, University of Dammam, Dammam 31451, Kingdom of Saudi Arabia Department of Medicine, Boston University School of Medicine, Boston 02118, MA, USA.
authors.forename: Alawi
authors.initials: A
authors.lastname: Habara
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston 02118, MA, USA mhsteinb@bu.edu.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005319:Fetal Hemoglobin / Q000032:analysis / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D012720:Severity of Illness Index
chemical_list: D005319:Fetal Hemoglobin
keywords: Severity in sickle cell disease; genome-wide association study; genotype–phenotype correlation; hemolysis; single nucleotide polymorphisms; subphenotypes of sickle cell disease