Abstract | BACKGROUND: A selective susceptibility of certain individuals to form multiple alloantibodies in response to red cell transfusion is well-recognized in clinical practice, and is a particular problem in persons with sickle cell disease (SCD). The reason for this differential susceptibility is unclear, but inter-individual genetic differences are likely to contribute. METHODS: We conducted a pilot case-control genome-wide association study using 1,000,000 SNPs in 94 alloimmune responders (cases) and non-responders (controls) with SCD in order to identify loci of large effect size associated with alloimmunization. RESULTS: No loci showed evidence of association at a genome-wide significance cut-off (p < 0.5 × 10(-8)). SNPs in the ARAP1/STARD10 region showed suggestive association (p < 1 × 10(-6)), but no association was observed at previously implicated loci TRIM21 or HLA. In analyses of the number of accumulated antibodies, a modest association was found with SNPs in the Toll-like receptor gene TLR10 (p < 1 × 10(-4)). CONCLUSIONS: Alloimmunization in persons with SCD is unlikely to be mediated by loci of very large effect size; however, larger and more comprehensive studies are required to fully evaluate loci with more moderate effects. This study provides a working approach to such future studies in SCD.
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Authors | Neil A Hanchard, Joann M Moulds, John W Belmont, Alice Chen |
Journal | Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie
(Transfus Med Hemother)
Vol. 41
Issue 6
Pg. 453-61
(Nov 2014)
ISSN: 1660-3796 [Print] Switzerland |
PMID | 25670933
(Publication Type: Journal Article)
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