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Genomewide association study of HLA alloimmunization in previously pregnant blood donors
Seielstad, M., Page, G. P., Gaddis, N., Lanteri, M., Lee, T.-H., Kakaiya, R., Barcellos, L. F., Criswell, L. A., Triulzi, D., Norris, P. J., Busch, M. P., & NHLBI REDS-III Study Investigators (2018). Genomewide association study of HLA alloimmunization in previously pregnant blood donors. Transfusion, 58(2), 402-412. https://doi.org/10.1111/trf.14402
BACKGROUNDAlloimmunization through blood transfusion, transplantation, or circulating fetal cells during pregnancy is a significant concern. Some exposed individuals make alloantibodies while others do not, implying variation in genetic risk factors.STUDY DESIGN AND METHODSWe conducted a genomewide association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to identify genetic variants for HLA alloimmunization in previously pregnant blood donors with (n=752) and without (n=753) HLA Class I or II alloantibodies.RESULTSA SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide significance (p=2.06x 10(-8)), with multiple adjacent markers p<10(-6), for women with anti-Class I alloantibodies only. Little is currently known about the function of NXPH2, although gene family members have been shown to impact immunity. SNPs in the E2F7 gene, a transcription factor related to cell cycle control and cellular proliferation, also approached genomewide significance (p=2.5x10(-7)).CONCLUSIONFurther work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.
