Abstract
BackgroundUnderstanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte.MethodsThis retrospective cohort study analyzed clinical and biological data, collected between January1st2007 and December 31st2017, in children younger than 18 years.ResultsWe included 185 children with 72% SS, 16% Sβ0-thalassemia and 12% Sβ + thalassemia. The average age was 9.5 years; 10% of patients were lost to follow up. The Bantu haplotype was associated with an increase in hospitalizations and transfusions. The alpha-thalassemic mutation was associated with a decrease of hemolysis biological parameters (anemia, reticulocytes), and a decrease of cerebral vasculopathy. The Single Nucleotide Polymorphisms BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were associated with the group of children with HbF > 10%. Patients with HbF > 10% presented a significant risk of early onset of cerebral vasculopathy.ConclusionsThe most remarkable result of our study was the association of SNPs with clinically relevant phenotypic groups. BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were correlated with HbF > 10%, a group that has a higher risk of cerebral vasculopathy and should be oriented towards the hemolytic sub-phenotype.
Highlights
Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte
Fetal hemoglobin (HbF) is associated with a high risk of cerebral vasculopathy Our survival analysis without occurrence of cerebral vasculopathy showed that the group of patients with HbF > 10% presented a significant risk of early onset of cerebral vasculopathy
Another study, conducted in Cameroon, showed identic allelic frequencies between a Cameroonian population and the African-American cohort, but a lower impact on HbF among Africans [51]. These results show the interest of looking for single nucleotide polymorphism (SNP) in a given population by performing Genome wide association study (GWAS), and not extrapolating the polymorphisms found in another population
Summary
Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte. Sickle cell disease (SCD) refers to a group of autosomal recessive genetic disorders characterized by the synthesis of an abnormal hemoglobin: sickle hemoglobin S (βs, HbS), results from the substitution of a single amino acid (Glu → Val) at the sixth position of β-chain of normal hemoglobin (HbA) molecule [1, 2]. This singlepoint mutation leads to the polymerization of the HbS molecule and red cell sickling under deoxygenated conditions. These processes can result in severe complications including chronic pain, downstream-organ dysfunction, stroke, life-long suffering, poor quality of life and early mortality
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