title: Differences in the clinical and genotypic presentation of sickle cell disease around the world.
abstract: Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. Cardiopulmonary complications are major causes of morbidity and mortality. Hemoglobin SS (Hb SS) represents a large proportion of SCD in the Americas, United Kingdom, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia in Greece and India. Coinheritance of α-thalassemia and persistence of hemoglobin F production are observed in highest frequency in certain regions of India and the Middle East. As confirmed in the PUSH and Walk-PHaSST studies, Hb SS, absence of co-inheriting alpha-thalassemia, and low hemoglobin F levels tend to be associated with more hemolysis, lower hemoglobin oxygen saturations, greater proportions of elevated tricuspid regurgitant jet velocity and brain natriuretic peptide, and increased left ventricular mass index. Identification of additional genetic modifiers will improve prediction of cardiopulmonary complications in SCD.
authors.affiliation: Comprehensive Sickle Cell Center, Section of Hematology-Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL. Electronic address: ssaraf@uic.edu.
authors.forename: Santosh L
authors.initials: SL
authors.lastname: Saraf
authors.affiliation: Comprehensive Sickle Cell Center, Section of Hematology-Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL; Jesse Brown VA Medical Center, Chicago IL.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Molokie
authors.affiliation: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.affiliation: Department of Pediatrics, Section of Cardiology, Children's National Medical Center, Washington DC.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Sable
authors.affiliation: Department of Pediatrics, Section of Hematology, Children's National Medical Center, Washington DC.
authors.forename: Lori
authors.initials: L
authors.lastname: Luchtman-Jones
authors.affiliation: Department of Pediatrics, Section of Cardiology, University of Michigan, Ann Arbor, MI.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Ensing
authors.affiliation: Department of Pediatrics, Section of Hematology, University of Michigan, Ann Arbor, MI.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.affiliation: Center for Sickle Cell Disease, Department of Pediatrics, Howard University, Washington DC.
authors.forename: Sohail R
authors.initials: SR
authors.lastname: Rana
authors.affiliation: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
authors.forename: Xiao M
authors.initials: XM
authors.lastname: Niu
authors.affiliation: Department of Medicine, Section of Pulmonary & Critical Care, University of Illinois Hospital and Health Sciences System, Chicago, IL.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.affiliation: Vascular Medicine Institute and the Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburg, PA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.affiliation: Comprehensive Sickle Cell Center, Section of Hematology-Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
mesh_terms: D000755:Anemia, Sickle Cell / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D005006:Ethnicity; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D014943:Global Health; D006801:Humans; D015994:Incidence; D009154:Mutation
chemical_list: D005319:Fetal Hemoglobin
keywords: Alpha thalassemia; Echocardiogram; Hemoglobin F; Pulmonary Function Test; Sickle Cell Disease