Serological and molecular genetic study of the Ael/AelB phenotype induced by the c. 575T>C variant in the ABO gene
10.13303/j.cjbt.issn.1004-549x.2026.07.016
- VernacularTitle:ABO基因c. 575T>C变异致Ael/AelB表型的血清学及分子遗传学研究
- Author:
Yanying DONG
1
;
Qinqin ZUO
2
;
Peixing XU
1
;
Minggang ZHANG
1
;
Xia JIANG
1
;
Zixuan WANG
1
;
Miao WANG
1
;
Gengyuan LIU
1
;
Yi DING
3
;
Tianju WANG
2
;
Junhui QUAN
1
Author Information
1. Department of Transfusion Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China
2. Shaanxi Blood Center, Xi'an Blood Center, Xi'an 710061, China
3. Department of Transfusion Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China
- Publication Type:Journal Article
- Keywords:
Ael/AelB subtype;
gene sequencing;
c. 575T>C mutation;
GTA activity;
pedigree investigation
- From:
Chinese Journal of Blood Transfusion
2026;39(7):922-927
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To analyze the serological phenotypes and molecular genetic characteristics of a proband with ABO forward and reverse typing discrepancy and their family members, and to investigate the molecular genetic mechanism underlying the Ael/AelB phenotype caused by the c. 575T>C variant on an ABO
A1.02 background. Methods: Serological testing and adsorption-elution assays were performed for blood group identification of the proband and family members. PCR-SBT, cloning sequencing, and Nanopore third-generation sequencing were used to analyze ABO gene variants and haplotypes. Phyre2 and PyMOL were used to predict the effect of the p. Ile192Thr variant on the structure of glycosyltransferase A (GTA), and plasma GTA activity was evaluated using an in vitro transferase assay. Results: Among thirteen family members, four members showed a serological phenotype consistent with the Ael subtype and one with the AelB subtype. Cloning sequencing and third-generation sequencing confirmed that five family members carried the ABO
A1.02 (c. 575T>C) variant, which co-segregated with the weak A phenotype in the family. Structural modeling suggested that p. Ile192Thr may alter the local spatial conformation and hydrogen-bond interactions of GTA. Plasma GTA activity testing showed markedly reduced GTA activity in the tested individuals. Conclusion: The ABO
A1.02 (c. 575T>C) variant is associated with the Ael/AelB phenotype. The p. Ile192Thr substitution may weaken A antigen expression by altering GTA conformation and reducing enzymatic activity. This study provides additional evidence for the role of this variant in the Ael/AelB phenotype from the perspectives of familial inheritance, full-length haplotype analysis, and functional assessment, which is important for accurate ABO subtype identification and individualized transfusion strategies.
