Acute Chest Syndrome is Associated with Single Nucleotide Polymorphism-defined Beta Globin Cluster Haplotype in Children with Sickle Cell Anaemia

Overview

Journal Br J Haematol

Specialty Hematology

Date 2013 Aug 20

PMID 23952145

Citations 10

Authors

Christopher J Bean

Sheree L Boulet

Genyan Yang

Amanda B Payne

Nafisa Ghaji

Meredith E Pyle

W Craig Hooper

Pallav Bhatnagar

Jeffrey Keefer

Emily A Barron-Casella

James F Casella

Michael R DeBaun

Affiliations

Soon will be listed here.

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 (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.

Citing Articles

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