Genomewide association study of HLA alloimmunization in previously pregnant blood donors
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.
Seielstad, M., Page, G. P., Gaddis, N., Lanteri, M., Lee, T-H., Kakaiya, R., ... NHLBI REDS-III Study Investigators (2017). Genomewide association study of HLA alloimmunization in previously pregnant blood donors. Transfusion, 58(2), 402-412. DOI: 10.1111/trf.14402