Effect of variants in the non-coding region of ABO blood group alleles on the weak expression of antigens
10.3760/cma.j.cn511374-20241113-00590
- VernacularTitle:ABO血型等位基因非编码区变异对抗原弱表达的影响
- Author:
Hua WANG
1
;
Yunxiang WU
1
;
Fei WANG
1
;
Yajun LIANG
1
;
Qing LI
1
;
Jiangtao ZUO
1
;
Yi XU
1
;
Zhicheng LI
1
;
Ruiqing GUO
1
;
Xin ZHANG
1
;
Demei ZHANG
1
Author Information
1. 太原市血液中心(太原市输血技术研究所)，太原 030024
- Publication Type:Journal Article
- Keywords:
ABO blood-group system;
Weak expression of antigen;
Non-coding region;
Long read sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(5):628-632
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the regulatory mechanisms underlying the weak expression of ABO blood group antigens due to variants in the non-coding regions of the ABO gene. Methods:From June 2014 to October 2023, a total of 29 samples from the Taiyuan Blood Center and local hospitals, which were serologically identified as having weak ABO antigen expression without detectable coding region mutations, were selected for this study. Full-length ABO gene sequencing was performed using third-generation long-read sequencing technology (Pacific Biosciences) to obtain complete haplotype sequences of the ABO gene. Variants in the non-coding regions were compared and identified to infer their regulatory effects on weak antigen expression. The procedures followed in this study were in accordance with the ethical standards of the World Medical Association′s Declaration of Helsinki (2013 revision). The Medical Ethics Committee of Taiyuan Blood Center has granted an exemption from ethical review. Results:18 bp deletions in the -35 to -18 region of the promoter were identified in 7 samples. Variants in intron 1 (+ 5.8 kb) were detected in 7 samples, including ABO* A (28+ 5792_5793delCT (1 case) and ABO* B (28+ 5793T>C) located in the GATA binding region; ABO* B (28+ 5808C>T) (1 case) in the E-box region; and ABO* B (28+ 5875C>T) (4 cases) in the RUNX1 binding region. Nucleotide variants at splice sites were detected in 2 samples, namely ABO* B (C.98+ 1G>A) and ABO* B (C.204-2A>C). Conclusion:Variants in the non-coding regulatory sequences of the ABO gene are a significant factor contributing to weak ABO antigen expression. In clinical ABO sequencing, it is essential to screen not only the conventional coding regions but also the flanking sequences, introns, and splice sites of the ABO gene to facilitate precise blood transfusion.
