与Jk(a +)弱抗原表型相关的JK*01 W.06等位基因中的启动子多态性。

Promoter polymorphisms in the JK*01 W.06 allele associated with the Jk(a + ) weak antigen phenotype.

作者信息

Liang Shuang, Wu Fan, Jiang Renhui, Liu Tong, Sun Liyan, Tang Rong, Dang Yingnan, Deng Zhihui

机构信息

Institute of Transfusion Medicine, Shenzhen Blood Center, Shenzhen, People's Republic of China.

Division of Business Management, Yunnan Kunming Blood Center, Kunming, China.

出版信息

BMC Immunol. 2025 Jun 8;26(1):43. doi: 10.1186/s12865-025-00727-2.

DOI:10.1186/s12865-025-00727-2

PMID:40484950

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12147333/

Abstract

BACKGROUND

The Kidd blood group system is critical in transfusion medicine, especially for delayed hemolytic reactions. However, the genetic background and molecular mechanisms underlying the weak antigen phenotype remain unclear. This study aimed to elucidate how the allelic variant and its promoter region polymorphisms contribute to reduced Jk antigen expression in the weak antigen phenotype.

METHODS

Serological techniques and flow cytometry identified 20 Jk(a + ) samples from 800 Han Chinese blood donors. Third-generation sequencing analyzed the gene haplotype sequences, quantifying the frequency of the allele and characterizing promoter sequence variations. Dual-luciferase assays assessed the differential transcriptional activities of two distinct promoter sequences, Promoter-A and Promoter-B.

RESULTS

In Jk(a + ) samples, the frequency of the allele reached 62.5%, significantly higher than that in random samples (34.7%). Analysis of the promoter region sequences revealed that 76.00% of Jk(a + ) samples displayed the Promoter-B polymorphism, whereas Promoter-A was predominant in Jk(a+) samples (76.09%). The dual-luciferase assay demonstrated that Promoter-A exhibited higher transcriptional activity compared to Promoter-B.

CONCLUSIONS

This study uncovers the association between the allelic variant and the Jk(a + ) phenotype, highlighting the pivotal role of promoter polymorphisms in potentially influencing the formation of the Jk(a + ) antigen through modulation of transcriptional activity.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12865-025-00727-2.

摘要

背景

基德血型系统在输血医学中至关重要，尤其是对于迟发性溶血性反应。然而，弱抗原表型背后的遗传背景和分子机制仍不清楚。本研究旨在阐明等位基因变异及其启动子区域多态性如何导致弱抗原表型中Jk抗原表达降低。

方法

血清学技术和流式细胞术从800名汉族献血者中鉴定出20份Jk(a+)样本。第三代测序分析基因单倍型序列，量化等位基因频率并表征启动子序列变异。双荧光素酶测定评估两种不同启动子序列Promoter-A和Promoter-B的差异转录活性。

结果

在Jk(a+)样本中，等位基因频率达到62.5%，显著高于随机样本中的频率(34.7%)。对启动子区域序列的分析表明，76.00%的Jk(a+)样本表现出Promoter-B多态性，而Promoter-A在Jk(a+)样本中占主导地位(76.09%)。双荧光素酶测定表明，与Promoter-B相比，Promoter-A表现出更高的转录活性。