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- W2564220852 abstract "Abstract Aplastic anemia (AA) is a heterogeneous disease characterized by bone marrow aplasia and peripheral blood pancytopenia, a profound deficit of hematopoietic stem and progenitor cells. Notch4 is structurally distinct from Notch1 through Notch3. Notch4 signaling plays a role in lineage commitment in hematopoiesis. Therefore, we hypothesized that Notch4 polymorphisms could potentially influence the expression level of Notch4 protein and associate with the risk of AA. To investigate the role of the two Notch4 rs2071282 (+2763 C>T, Pro204Leu) and 422951(+3323 A>G, Thr320Ala) polymorphisms in susceptibility to AA, we genotyped in 151 AA patients and 552 healthy control subjects using PCR-RFLP and quantified expression of Notch4. We previously reported that Notch4 +2763 CT genotype is significantly associated with increased risk for AA (odds ratios (OR) = 1.77; 95% confidence intervals (CI) = 1.05–2.98, p=0.032) and the haplotype CG is significantly associated with the risk of AA (OR= 0.70 95% CI 0.50–0.98, p= 0.037) (The American Society of Hematology 2006. 12. poster). With quantified expression level of Notch4 using quantitative SYBR green methods, we identified a significant positive correlation between +2763 C>T and +3323 A>G each genotype and transcription level (p<0.0001) in AA. With quantified expression level of Jagged 1, we also identified a significant positive correlation between +2763 C>T and +3323 A>G each genotype and transcription level (p<0.0001) in AA. To the effect of the SNP on transcription, we also carried out allelic imbalance using allelic quantification mode pyrosequencing method. The mean ratio was 1.7, higher than that of controls cDNA and DNA amplicons of AA (ratio=1.3, P < 0.001) in the 16 heterozygotes AA and 25 contrrols with genotype +3323 A/G, but there was no significance correlation in heterozygotes with genotype +2763 C>T. In conclusion, our results suggest that regulation of expression Notch4 by two polymorphisms may play an important role in the susceptibility to AA." @default.
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- W2564220852 date "2007-11-16" @default.
- W2564220852 modified "2023-09-27" @default.
- W2564220852 title "Functional Polymorphisms of Notch 4 and the Risk of Aplastic Anemia." @default.
- W2564220852 doi "https://doi.org/10.1182/blood.v110.11.1732.1732" @default.
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