We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia.
- Authors
Bean, Christopher J.; Boulet, Sheree L.; Yang, Genyan; Payne, Amanda B.; Ghaji, Nafisa; Pyle, Meredith E.; Hooper, W. Craig; Bhatnagar, Pallav; Keefer, Jeffrey; Barron‐Casella, Emily A.; Casella, James F.; DeBaun, Michael R.
- Abstract
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 (Hb SS). 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 βS-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 βS-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 βS-haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA.
- Subjects
ACUTE chest syndrome; SINGLE nucleotide polymorphisms; GLOBIN; HAPLOTYPES; SICKLE cell anemia in children
- Publication
British Journal of Haematology, 2013, Vol 163, Issue 2, p268
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.12507