Seielstad Mark, Page Grier P, Gaddis Nathan, Lanteri Marion, Lee Tzong-Hae, Kakaiya Ram, Barcellos Lisa F, Criswell Lindsey A, Triulzi Darrell, Norris Philip J, Busch Michael P
Blood Systems Research Institute, University of California San Francisco, San Francisco, California.
Institute for Human Genetics, University of California San Francisco, San Francisco, California.
Transfusion. 2018 Feb;58(2):402-412. doi: 10.1111/trf.14402. Epub 2017 Nov 22.
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.
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.
A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide significance (p = 2.06 × 10 ), with multiple adjacent markers p < 10 , 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 ).
Further work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.
孕期通过输血、移植或循环胎儿细胞发生的同种免疫是一个重大问题。一些暴露个体产生同种抗体，而另一些则不产生，这意味着遗传风险因素存在差异。
我们对9427497个单核苷酸多态性（SNP）进行了全基因组关联研究（GWAS），以确定既往有（n = 752）和无（n = 753）HLA I类或II类同种抗体的妊娠献血者中HLA同种免疫的遗传变异。
仅对于有抗I类同种抗体的女性，神经纤毛蛋白2（NXPH2）基因中的一个SNP超过全基因组显著性水平（p = 2.06×10 ），多个相邻标记p < 10 。目前对NXPH2的功能了解甚少，尽管已表明该基因家族成员会影响免疫。E2F7基因中的SNP，一种与细胞周期控制和细胞增殖相关的转录因子，也接近全基因组显著性水平（p = 2.5×10 ）。
有必要进一步开展工作，扩展GWAS方法，并在同种抗体形成的背景下对NXPH2和E2F7中的变异进行表征。
