RGD Reference Report - Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia. - Rat Genome Database
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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.
RGD ID: 10449047
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.

Annotation

Disease Annotations    
acute chest syndrome  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Hbb  (hemoglobin subunit beta)

Genes (Homo sapiens)
HBB  (hemoglobin subunit beta)


Additional Information