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

Authors: 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 
Citation: Bean CJ, etal., Br J Haematol. 2013 Oct;163(2):268-76. doi: 10.1111/bjh.12507. Epub 2013 Aug 16.
Pubmed: (View Article at PubMed) PMID:23952145
DOI: Full-text: DOI:10.1111/bjh.12507

Genetic diversity at the human beta-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 beta-globin locus have not been consistently associated with clinical phenotypes. To define the genetic structure at the beta-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 (beta-globin gene) cluster. We identified three predominant haplotypes accounting for 96% of the beta(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 beta(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 beta(S) -haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA.

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CRRD ID: 10449047
Created: 2015-12-15
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Last Modified: 2015-12-15
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.