Genetic Modifiers of Sickle Cell Disease: A Genotype-Phenotype Relationship Study in a Cohort of 82 Children on Mayotte Island. (June 2015)

• Record Type: Journal Article
• Authors: Muszlak, Mathias; Pissard, Serge; Badens, Catherine; Chamouine, Abdourahim; Maillard, Olivier; Thuret, Isabelle
• Is Part Of: Hemoglobin. Volume 39:Number 3(2015)
• Page Start: 156
• Page End: 161
• Publication Date: 2015-06
• Subjects: Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.3109/03630269.2015.1023897
• Languages: English
• ISSNs: 0363-0269

Abstract

<abstract> <title>Abstract</title> <p>Sickle cell disease presents a great clinical variability that remains largely misunderstood. New disease protective genetic modifiers acting mainly through an increased Hb F level have recently been described. We studied relations between clinical and hematological phenotypes and known sickle cell disease genetic modifiers in patients from Mayotte Island, a remote French territory located in the Indian Ocean. Eighty-two children with sickle cell disease were enrolled; their median age was 5.9 years (range 1-18). Clinical and hematological features of sickle cell disease were retrospectively collected. Genetic studies included determination of β-globin genotypes [Hb SS, Hb S-β<sup>0</sup>-thalassemia (Hb S-β<sup>0</sup>-thal), Hb S-β<sup>+</sup>-thal], β<sup>S</sup>-globin locus haplotype, α-thalassemia (α-thal), and single nucleotide polymorphisms (SNPs) located in quantitative trait loci for Hb F expression (<italic>Xmn</italic>I polymorphism, <italic>BCL11A</italic> rs4671393 and rs11886868, intergenic region of <italic>HBS1L-MYB</italic> rs28384513, rs4895441 and rs9399137). Univariate and multivariate analyses were conducted. Twenty-eight percent of the patients had Hb S-β-thal (eight different mutations in 21 patients), 55.0% had the −α<sup>3.7</sup> (rightward) deletion and 88.0% of the homozygous Hb SS patients were carrying a homozygous Bantu haplotype. In the multivariate model, the prognosis role of the SNP <italic>BCL11A</italic> rs4671393 was confirmed in the studied population showing a significant association with an elevated Hb F level and with a low hospitalization rate. The −α<sup>3.7</sup> deletion<italic>, Xmn</italic>I polymorphism and intergenic region <italic>HBS1L-MYB</italic> SNPs were not significantly linked to any clinical criteria of severity. This report, the first to describe the main features of children with sickle cell disease on Mayotte Island, highlights the protective effect of the <italic>BCL11A</italic> polymorphism in this population.</p> </abstract>