In:
Transfusion Medicine and Hemotherapy, S. Karger AG, Vol. 50, No. 4 ( 2023), p. 263-269
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 The molecular diagnosis of the A 〈 sub 〉 1 〈 /sub 〉 blood group is based on the exclusion of 〈 i 〉 ABO 〈 /i 〉 gene variants causing blood groups A 〈 sub 〉 2 〈 /sub 〉 , B, or O. A specific genetic marker for the A 〈 sub 〉 1 〈 /sub 〉 blood group is still missing. Recently, long-read ABO sequencing revealed four sequence variations in intron 1 as promising markers for the 〈 i 〉 ABO 〈 /i 〉 * 〈 i 〉 A1 〈 /i 〉 allele. Here, we evaluated the diagnostic values of the 4 variants in blood donors with regular and weak A phenotypes and genotypes. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 ABO phenotype data (A, B, AB, or O) were taken from the blood donor files. The 〈 i 〉 ABO 〈 /i 〉 genotypes (low resolution) were known from a previous study and included the variants c.261delG, c.802G & #x3e;A, c.803G & #x3e;C, and c.1061delC. 〈 i 〉 ABO 〈 /i 〉 variant alleles ( 〈 i 〉 ABO 〈 /i 〉 * 〈 i 〉 AW.06, 〈 /i 〉 * 〈 i 〉 AW.08, 〈 /i 〉 * 〈 i 〉 AW.09, 〈 /i 〉 * 〈 i 〉 AW.13 〈 /i 〉 , * 〈 i 〉 AW.30 〈 /i 〉 , and * 〈 i 〉 A3.02 〈 /i 〉 ) were identified in weak A donors by sequencing the 〈 i 〉 ABO 〈 /i 〉 exons before. For genotyping of the 〈 i 〉 ABO 〈 /i 〉 intron 1 variants rs532436, rs1554760445, rs507666, and rs2519093, we applied TaqMan assays with endpoint fluorescence detection according to a standard protocol. Genotypes of the variants were compared with the ABO phenotype and genotype. Evaluation of diagnostic performance included sensitivity, specificity, positive (PPV), and negative predictive value (NPV). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In 1,330 blood donors with regular ABO phenotypes and genotypes, the intron 1 variants were significantly associated with the proposed A 〈 sub 〉 1 〈 /sub 〉 blood group. In 15 donors, we found discrepancies to the genotype of at least one of the 4 variants. For the diagnosis of the ABO*A1 allele, the variants showed 98.79–99.48% sensitivity, 99.66–99.81% specificity, 98.80–99.31% PPV, and 99.66–99.86% NPV. Regarding the A phenotype, the diagnostic values were 99.02–99.41% sensitivity, 99.63–99.76% specificity, 99.41–99.61% PPV, and 99.39–99.63% NPV. The * 〈 i 〉 A1 〈 /i 〉 marker allele of all intron 1 variants was also associated with the * 〈 i 〉 AW.06 〈 /i 〉 , * 〈 i 〉 AW.13 〈 /i 〉 , and * 〈 i 〉 AW.30 〈 /i 〉 variants. Samples with * 〈 i 〉 AW.08 〈 /i 〉 , * 〈 i 〉 AW.09 〈 /i 〉 , and * 〈 i 〉 A3.02 〈 /i 〉 variants lacked this association. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The 〈 i 〉 ABO 〈 /i 〉 intron 1 variants revealed significant association with the 〈 i 〉 ABO 〈 /i 〉 * 〈 i 〉 A1 〈 /i 〉 allele and the A phenotype. However, the intron 1 genotype does not exclude variant alleles causing weak A phenotypes. With the introduction of reliable tag, single nucleotide variants for the A 〈 sub 〉 1 〈 /sub 〉 , A 〈 sub 〉 2 〈 /sub 〉 , B, and O blood groups and the genotyping instead of phenotyping of the ABO blood group are getting more feasible on a routine basis.
Type of Medium:
Online Resource
ISSN:
1660-3796
,
1660-3818
Language:
English
Publisher:
S. Karger AG
Publication Date:
2023
detail.hit.zdb_id:
2100533-3
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