{"title":"评估ABO基因内含子1中的单核苷酸变体作为A1血型的诊断标记。","authors":"Peter Bugert, Gabi Rink, Harald Klüter","doi":"10.1159/000528683","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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>A, c.803G>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/85/tmh-0050-0263.PMC10521232.pdf","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Single Nucleotide Variants in Intron 1 of the ABO Gene as Diagnostic Markers for the A<sub>1</sub> Blood Group.\",\"authors\":\"Peter Bugert, Gabi Rink, Harald Klüter\",\"doi\":\"10.1159/000528683\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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>A, c.803G>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":23252,\"journal\":{\"name\":\"Transfusion Medicine and Hemotherapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/85/tmh-0050-0263.PMC10521232.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transfusion Medicine and Hemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000528683\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transfusion Medicine and Hemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000528683","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Evaluation of Single Nucleotide Variants in Intron 1 of the ABO Gene as Diagnostic Markers for the A1 Blood Group.
Introduction: The molecular diagnosis of the A1 blood group is based on the exclusion of ABO gene variants causing blood groups A2, B, or O. A specific genetic marker for the A1 blood group is still missing. Recently, long-read ABO sequencing revealed four sequence variations in intron 1 as promising markers for the ABO*A1 allele. Here, we evaluated the diagnostic values of the 4 variants in blood donors with regular and weak A phenotypes and genotypes.
Methods: ABO phenotype data (A, B, AB, or O) were taken from the blood donor files. The ABO genotypes (low resolution) were known from a previous study and included the variants c.261delG, c.802G>A, c.803G>C, and c.1061delC. ABO variant alleles (ABO*AW.06,*AW.08,*AW.09,*AW.13, *AW.30, and *A3.02) were identified in weak A donors by sequencing the ABO exons before. For genotyping of the ABO 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).
Results: In 1,330 blood donors with regular ABO phenotypes and genotypes, the intron 1 variants were significantly associated with the proposed A1 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 *A1 marker allele of all intron 1 variants was also associated with the *AW.06, *AW.13, and *AW.30 variants. Samples with *AW.08, *AW.09, and *A3.02 variants lacked this association.
Conclusion: The ABO intron 1 variants revealed significant association with the ABO*A1 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 A1, A2, B, and O blood groups and the genotyping instead of phenotyping of the ABO blood group are getting more feasible on a routine basis.
期刊介绍：
This journal is devoted to all areas of transfusion medicine. These include the quality and security of blood products, therapy with blood components and plasma derivatives, transfusion-related questions in transplantation, stem cell manipulation, therapeutic and diagnostic problems of homeostasis, immuno-hematological investigations, and legal aspects of the production of blood products as well as hemotherapy. Both comprehensive reviews and primary publications that detail the newest work in transfusion medicine and hemotherapy promote the international exchange of knowledge within these disciplines. Consistent with this goal, continuing clinical education is also specifically addressed.
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