Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia.

Bean CJ, Boulet SL, Yang G, Payne AB, Ghaji N, Pyle ME, Hooper WC, Bhatnagar P, Keefer J, Barron-Casella EA, Casella JF, Debaun MR
Br J Haematol. 2013 163 (2): 268-76

PMID: 23952145 · PMCID: PMC4026174 · DOI:10.1111/bjh.12507

Genetic diversity at the human β-globin locus has been implicated as a modifier of sickle cell anaemia (SCA) severity. However, haplotypes defined by restriction fragment length polymorphism sites across the β-globin locus have not been consistently associated with clinical phenotypes. To define the genetic structure at the β-globin locus more thoroughly, we performed high-density single nucleotide polymorphism (SNP) mapping in 820 children who were homozygous for the sickle cell mutation (HbSS). Genotyping results revealed very high linkage disequilibrium across a large region spanning the locus control region and the HBB (β-globin gene) cluster. We identified three predominant haplotypes accounting for 96% of the β(S) -carrying chromosomes in this population that could be distinguished using a minimal set of common SNPs. Consistent with previous studies, fetal haemoglobin level was significantly associated with β(S) -haplotypes. After controlling for covariates, an association was detected between haplotype and rate of hospitalization for acute chest syndrome (ACS) (incidence rate ratio 0·51, 95% confidence interval 0·29-0·89) but not incidence rate of vaso-occlusive pain or presence of silent cerebral infarct (SCI). Our results suggest that these SNP-defined β(S) -haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA.

© 2013 John Wiley & Sons Ltd.

MeSH Terms (16)

Acute Chest Syndrome Adolescent Alleles Anemia, Sickle Cell beta-Globins Child Child, Preschool Female Fetal Hemoglobin Haplotypes Humans Linkage Disequilibrium Male Multigene Family Patient Admission Polymorphism, Single Nucleotide

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