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人类 Gb3/CD77 合酶的 A4GALT 刺突额外产物中的单核苷酸多态性,是 P1PK 血型系统的基础。

Single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system.

机构信息

Laboratory of Glycobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.

Faculty of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland.

出版信息

PLoS One. 2018 Apr 30;13(4):e0196627. doi: 10.1371/journal.pone.0196627. eCollection 2018.

Abstract

Contrary to the mainstream blood group systems, P1PK continues to puzzle and generate controversies over its molecular background. The P1PK system comprises three glycosphingolipid antigens: Pk, P1 and NOR, all synthesised by a glycosyltransferase called Gb3/CD77 synthase. The Pk antigen is present in most individuals, whereas P1 frequency is lesser and varies regionally, thus underlying two common phenotypes: P1, if the P1 antigen is present, and P2, when P1 is absent. Null and NOR phenotypes are extremely rare. To date, several single nucleotide polymorphisms (SNPs) have been proposed to predict the P1/P2 status, but it has not been clear how important they are in general and in relation to each other, nor has it been clear how synthesis of NOR affects the P1 phenotype. Here, we quantitatively analysed the phenotypes and A4GALT transcription in relation to the previously proposed SNPs in a sample of 109 individuals, and addressed potential P1 antigen level confounders, most notably the red cell membrane cholesterol content. While all the SNPs were associated with the P1/P2 blood type and rs5751348 was the most reliable, we found large differences in P1 level within groups defined by their genotype and substantial intercohort overlaps, which shows that the P1PK blood group system still eludes full understanding.

摘要

与主流血型系统不同,P1PK 因其分子背景仍令人费解并引发争议。P1PK 系统由三种糖脂抗原组成:Pk、P1 和 NOR,它们均由一种称为 Gb3/CD77 合酶的糖基转移酶合成。Pk 抗原存在于大多数个体中,而 P1 的频率较低且具有区域性差异,因此存在两种常见表型:P1,若存在 P1 抗原;P2,若不存在 P1 抗原。Null 和 NOR 表型极为罕见。迄今为止,已经提出了几种单核苷酸多态性(SNP)来预测 P1/P2 状态,但尚不清楚它们在一般情况下以及彼此之间的重要性,也不清楚 NOR 的合成如何影响 P1 表型。在这里,我们在 109 名个体的样本中定量分析了表型和 A4GALT 转录与先前提出的 SNPs 的关系,并解决了潜在的 P1 抗原水平混杂因素,尤其是红细胞膜胆固醇含量。虽然所有 SNP 均与 P1/P2 血型相关,且 rs5751348 最可靠,但我们发现同一基因型个体的 P1 水平存在较大差异,且不同队列之间存在大量重叠,这表明 P1PK 血型系统仍未被完全理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6625/5927444/29fd44a8545a/pone.0196627.g001.jpg

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