Genomewide association study of HLA alloimmunization in previously pregnant blood donors.

Pubmed ID: 29168253

Pubmed Central ID: PMC5803399

Journal: Transfusion

Publication Date: Feb. 1, 2018

MeSH Terms: Humans, Adult, Female, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Blood Donors, Neuropeptides, Isoantibodies, Pregnancy, E2F7 Transcription Factor, Fetomaternal Transfusion, Glycoproteins

Grants: HHSN268201100005C, HHSN268201100006C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN268201100005G, HHSN268201100005I, HHSN268201100001I, HHSN268201100002I, HHSN268201100004I, R21 HL124260

Authors: Busch MP, Lee TH, Triulzi D, Kakaiya R, Norris PJ, Seielstad M, Page GP, Gaddis N, Lanteri M, Barcellos LF, Criswell LA

Cite As: Seielstad M, Page GP, Gaddis N, Lanteri M, Lee TH, Kakaiya R, Barcellos LF, Criswell LA, Triulzi D, Norris PJ, Busch MP, NHLBI REDS-III Study Investigators. Genomewide association study of HLA alloimmunization in previously pregnant blood donors. Transfusion 2018 Feb;58(2):402-412. Epub 2017 Nov 22.

Studies:

Abstract

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<sup>-8</sup> ), with multiple adjacent markers p &lt; 10<sup>-6</sup> , 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<sup>-7</sup> ). CONCLUSION: Further work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.