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.
Methods
We conducted a genome-wide 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 genome-wide 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.