2023 Fiscal Year Final Research Report

Elucidation of ABO regulation through topological alteration of chromatin structure

Research Project

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Project/Area Number	19H03916
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 58040:Forensics medicine-related
Research Institution	Gunma University
Principal Investigator	Kominato Yoshihiko 群馬大学, 大学院医学系研究科, 教授 (30205512)
Co-Investigator(Kenkyū-buntansha)	窪理英子群馬大学, 医学部, 技術職員 (40747127) 高橋遥一郎筑波大学, 医学医療系, 教授 (50640538) 佐野利恵群馬大学, 大学院医学系研究科, 准教授 (70455955) 早川輝群馬大学, 大学院医学系研究科, 講師 (90758575)
Project Period (FY)	2019-04-01 – 2024-03-31
Keywords	ABO遺伝子
Outline of Final Research Achievements	The ABO blood group system is composed of the carbohydrate antigens A and B, as well as their antibodies, and is fundamental to the safety of blood transfusion. The blood groups were discovered at the beginning of the 20th century, and 90 years later Dr. Yamamoto at the Biomembrane Institute, University of Washington, reported the molecular basis of the ABO gene. Subsequently, we have clarified the transcriptional regulation of the gene expression including the cell type-independent promoter, and the cell type-specific control regions for erythroid or epithelial cells. Many variants in the promoter and erythroid cell-specific region have been reported in individuals with weak variants such as Bm, Am, B3, and A3. In addition, DNA methylation of the promoter was found to be involved in antigen reduction in cancer cells and mutations of the transcriptional factors involved in the ABO regulation were reported to be associated with antigen reduction on RBCs in leukemia patients.
Free Research Field	法医学
Academic Significance and Societal Importance of the Research Achievements	ABO遺伝子の転写調節機構が解明されたことにより、ABO遺伝子の転写調節領域とコード領域の解析が血液型検査に応用されるところとなり、赤血球表面上の血液型抗原量が減少する亜型に対する遺伝子解析がより精度を増すこととなった。一方、白血病患者においては血液型検査においてオモテ試験とウラ試験の不一致である例が経験されるが、ABO遺伝子の転写調節機構の解明によりその原因が明らかにされてきた。以上は、安全な輸血医療に貢献するものとなっている。