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Annals of Hematology

, Volume 97, Issue 9, pp 1695–1700 | Cite as

Ethnicity-specific impact of HLA I/II genotypes on the risk of inhibitor development: data from Korean patients with severe hemophilia A

  • Hyun-Young Kim
  • Jin-Hee Cho
  • Hee-Jung Kim
  • Hae-Sun Chung
  • Sun-Hee Kim
  • Ki-O Lee
  • Soo-Young Jung
  • Ki-Young Yoo
  • Hee-Jin Kim
Original Article

Abstract

Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.

Keywords

Hemophilia A Inhibitor HLA genotypes Mutation Korea 

Notes

Funding information

This study was supported by a grant from the Korea Food & Drug Administration (KFDA) and by a grant from Korea Hemophilia Foundation.

Compliance with ethical standards

This study was approved by the Institutional Review Board of Samsung Medical Center (Seoul, Korea), and all patients gave written informed consent in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2018_3358_MOESM1_ESM.docx (44 kb)
ESM 1 (DOCX 44 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hyun-Young Kim
    • 1
    • 2
  • Jin-Hee Cho
    • 1
  • Hee-Jung Kim
    • 1
    • 3
  • Hae-Sun Chung
    • 1
    • 4
  • Sun-Hee Kim
    • 1
  • Ki-O Lee
    • 5
  • Soo-Young Jung
    • 6
  • Ki-Young Yoo
    • 6
  • Hee-Jin Kim
    • 1
  1. 1.Department of Laboratory Medicine & Genetics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Department of Laboratory Medicine, Gyeongsang National University HospitalGyeongsang National University School of MedicineJinjuSouth Korea
  3. 3.Department of Laboratory Medicine, CHA Gangnam Medical CenterCHA University School of MedicineSeoulSouth Korea
  4. 4.Department of Laboratory MedicineEwha Womans University College of MedicineSeoulSouth Korea
  5. 5.Samsung Biomedical Research InstituteSamsung Medical CenterSeoulSouth Korea
  6. 6.Korea Hemophilia FoundationSeoulSouth Korea

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