Polymorphisms in MAPK9 (rs4147385) and CSF1R (rs17725712) are associated with the development of inhibitors in patients with haemophilia A in North China

Int J Lab Hematol. 2019 Aug;41(4):572-577. doi: 10.1111/ijlh.13055. Epub 2019 May 31.

Abstract

Introduction: The formation of neutralizing antibodies (FVIII inhibitors) in haemophilia A patients is an immune response to the deficient factor. This process is multifactorial and includes environmental and genetic factors. Some genetic markers that play a decisive role in the immune response have been identified as risk factors for inhibitor development.

Objective: Our aim was to investigate the association between polymorphisms in several genes involved in the regulation of the immune response and inhibitor development in patients with haemophilia A in North China.

Methods: We analysed eight SNPs (MAPK9 rs4147385, CSF1R rs17725712, CD44 rs927335, STAT4 rs7574865, IKZF1 rs4917014, ETS1 rs6590330, BANK1 rs17266594 and rs10516487) by Snapshot SNP genotyping assays in 100 haemophilia A patients, including 29 with inhibitors and 71 without inhibitors.

Results: Our results demonstrated that the rs17725712 A allele and the AA homozygous genotype of CSF1R were more frequent in patients with inhibitors. The rs4147385 G allele in MAPK9 was also more frequent in the inhibitor cohort.

Conclusion: We confirmed an association of CSF1R rs17725712 and MAPK9 rs4147385 with inhibitor development in haemophilia A patients in North China.

Keywords: haemophilia; immune response; inhibitors; polymorphisms; risk factors.

Publication types

  • Clinical Trial

MeSH terms

  • Alleles*
  • Antibodies, Neutralizing / blood
  • Asian People
  • Autoantibodies / blood
  • Blood Coagulation Factor Inhibitors / blood*
  • China
  • Factor VIII / antagonists & inhibitors*
  • Factor VIII / genetics
  • Factor VIII / metabolism
  • Hemophilia A / blood
  • Hemophilia A / genetics
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase 9 / genetics*
  • Polymorphism, Single Nucleotide*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics*

Substances

  • Antibodies, Neutralizing
  • Autoantibodies
  • Blood Coagulation Factor Inhibitors
  • CSF1R protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • F8 protein, human
  • Factor VIII
  • Mitogen-Activated Protein Kinase 9