2006 Fiscal Year Final Research Report Summary
Screening for causative genes in unknown hemolytic anemia
| Project/Area Number |
17591013
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
FUJII Hisaichi Tokyo Woman's Medical University, School of Medicine, Professor, 医学部, 教授 (70107762)
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| Co-Investigator(Kenkyū-buntansha) |
KANNO Hitoshi Tokyo Woman's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (70221207)
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| Project Period (FY) |
2005 – 2006
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| Keywords | α-hemoglobin stabilizing protein / hemolytic anemia / acute hemolysis / single nucleotide polymorphisms (SNPs) / oxidative stress / antioxidant |
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| Research Abstract |
Alpha-hemoglobin stabilizing protein (AHSP) binds specifically to α-hemoglobin, and prevents its precipitation in red blood cells (RBC). AHSP plays an important role as a molecular chaperone in the stabilization of unstable free α-globin monomer, which generates reactive oxygen species, resulting in damage to red cell protein and lipids. To examine that AHSP gene defects might account for either Heinz body-positive anemia or acute hemolytic anemia triggered by infection or drug administration, we performed a case-control study by examining seven SNPs (single nucleotide polymorphisms) of 28 hemolytic anemia patients and 95 controls, and found that a certain haplotype of the human AHSP gene had significant association with a subgroup of unknown hemolytic anemia. The haplotype included four SNPs (-557G,-465T,-201G and +248A) and a deletion-insertion polymorphism (DIP), T15, in 5'-flanking region of AHSP gene, and a reporter gene assay showed that the haplotype accounts for about 23% transcriptional activity of a control haplotype. In vitro mutagenesis analysis revealed that both the SNP-201G and T15 are responsible for decreased transcriptional activity of AHSP gene. We conclude that the AHSP gene is correlated to disease-susceptibility in a group of hemolytic anemia with either Heinz body-positive RBC or infection/drug-induced episodes, and that the homozygotes of-201A/T15 are more susceptible to oxidative stress.
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