Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA ; ARS/USDA/Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Scientific Support Services, LifeShare Blood Centers, Shreveport, LA, USA.
Transfus Med Hemother. 2014 Nov;41(6):453-61. doi: 10.1159/000369079. Epub 2014 Nov 7.
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.
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.
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)).
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.
在临床实践中，人们已经认识到某些个体对红细胞输注产生多种同种异体抗体的选择性易感性，这在镰状细胞病（SCD）患者中是一个特殊的问题。这种差异易感性的原因尚不清楚，但个体间的遗传差异可能起作用。
我们对 94 名 SCD 患者中的 100 万个 SNP 进行了一项先导性病例对照全基因组关联研究，以确定与同种免疫相关的大效应量基因座。
没有发现任何在全基因组显著水平（p < 0.5 × 10(-8))有显著关联的基因座。ARAP1/STARD10 区域的 SNPs 显示出有意义的关联（p < 1 × 10(-6))，但在先前涉及的 TRIM21 或 HLA 基因座未观察到关联。在对累积抗体数量的分析中，Toll 样受体基因 TLR10 中的 SNPs 显示出适度的关联（p < 1 × 10(-4))。
SCD 患者的同种免疫不太可能由非常大效应量的基因座介导；然而，需要更大和更全面的研究来充分评估具有更中等效应的基因座。本研究为 SCD 患者的未来研究提供了一种可行的方法。
