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Genomewide association study of HLA alloimmunization in previously pregnant blood donors
Author(s) -
Seielstad Mark,
Page Grier P.,
Gaddis Nathan,
Lanteri Marion,
Lee TzongHae,
Kakaiya Ram,
Barcellos Lisa F.,
Criswell Lindsey A.,
Triulzi Darrell,
Norris Philip J.,
Busch Michael P.
Publication year - 2018
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.14402
Subject(s) - human leukocyte antigen , single nucleotide polymorphism , genome wide association study , snp , context (archaeology) , immunology , genetic association , biology , genetics , gene , medicine , genotype , antigen , paleontology
BACKGROUND Alloimmunization 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 METHODS We 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. RESULTS A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome‐wide significance (p = 2.06 × 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 = 2.5 × 10 −7 ). CONCLUSION Further work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.