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SINGLE NUCLEOTIDE POLYMORPHISMS OF THE HIF1A GENE ARE ASSOCIATED WITH SENSITIVITY OF GLUCOCORTICOID TREATMENT IN PEDIATRIC ITP PATIENTS
Author(s): ,
Hao Gu
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
,
Xingjuan Xie
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
,
Jingyao Ma
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
,
Lingling Fu
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
,
Jie Ma
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
,
Runhui Wu
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
Zhenping Chen
Affiliations:
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Chine;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,China;Beijing Children's Hospital, Capital Medical University, National Center for Children's Health,Beijing,Cina;Beijing Children's Hospital, Capital Medical University, National Center f
(Abstract release date: 05/12/22) EHA Library. Gu H. 06/10/22; 358497; P1640
Dr. Hao Gu
Dr. Hao Gu
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1640

Type: Poster presentation

Session title: Platelet disorders

Background
Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases,suggesting that HIF1α may be involved in immune dysregulation in patients with immune thrombocytopenia (ITP). 

Aims
The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to ITP and its clinical prognosis including incidence of chronic immune thrombocytopenia (CITP) and glucocorticoid sensitivity.

Methods
This study involved 197 Chinese ITP pediatric patients (discovery cohort) and 220 healthy controls. The Sequenom MassArray system (Sequenom, San Diego, CA) was used to detect three SNPs genotypes in the  HIF1A gene: rs11549465, rs1957757 and rs2057482. We also employed another ITP cohort (N = 127) to validate the significant results of SNPs found in the discovery cohort.

Results
The frequencies of the three SNPs did not show any significant differences between the ITP and healthy control groups. The CT genotype at rs11549465 was significantly higher in ITP patients sensitive to glucocorticoid-treatment than in those insensitive to glucocorticoid-treatment (P = .025). These results were validated using another ITP cohort (N =127, P = .033). Moreover, the CC genotype was a risk factor for insensitive to GT the OR (95% confidence interval) was 5.96(5.23-6.69) in standard prednisone (PDN) (P=.0069) and 6.35(5.33-7.37) in high-dose dexamethasone (HDD) (P=.04).

Conclusion
Although HIF1A gene polymorphisms were not associated with susceptibility to ITP, the CT genotype at rs11549465 was associated with the sensitivity to glucocorticoid-treatment of ITP patients, suggesting that the rs11549465 SNP may contribute to the sensitivity of glucocorticoid treatment in pediatric ITP patients.

Keyword(s): Hypoxia-sensing, ITP, Pediatric, SNP

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1640

Type: Poster presentation

Session title: Platelet disorders

Background
Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases,suggesting that HIF1α may be involved in immune dysregulation in patients with immune thrombocytopenia (ITP). 

Aims
The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to ITP and its clinical prognosis including incidence of chronic immune thrombocytopenia (CITP) and glucocorticoid sensitivity.

Methods
This study involved 197 Chinese ITP pediatric patients (discovery cohort) and 220 healthy controls. The Sequenom MassArray system (Sequenom, San Diego, CA) was used to detect three SNPs genotypes in the  HIF1A gene: rs11549465, rs1957757 and rs2057482. We also employed another ITP cohort (N = 127) to validate the significant results of SNPs found in the discovery cohort.

Results
The frequencies of the three SNPs did not show any significant differences between the ITP and healthy control groups. The CT genotype at rs11549465 was significantly higher in ITP patients sensitive to glucocorticoid-treatment than in those insensitive to glucocorticoid-treatment (P = .025). These results were validated using another ITP cohort (N =127, P = .033). Moreover, the CC genotype was a risk factor for insensitive to GT the OR (95% confidence interval) was 5.96(5.23-6.69) in standard prednisone (PDN) (P=.0069) and 6.35(5.33-7.37) in high-dose dexamethasone (HDD) (P=.04).

Conclusion
Although HIF1A gene polymorphisms were not associated with susceptibility to ITP, the CT genotype at rs11549465 was associated with the sensitivity to glucocorticoid-treatment of ITP patients, suggesting that the rs11549465 SNP may contribute to the sensitivity of glucocorticoid treatment in pediatric ITP patients.

Keyword(s): Hypoxia-sensing, ITP, Pediatric, SNP

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