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

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.

LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway

“…It has been found that MAPK signaling pathway is involved in cell malignant phenotypes, including cell proliferation, cell differentiation and cell migration [ 20 ]. As a key member in the MAPK signaling pathway, MAPK9 is also correlated with several diseases, including non-small-cell lung carcinoma [ 21 ], haemophilia A [ 22 ], and type I diabetes [ 23 ]. Through our investigation, MAPK9 was discovered to be a downstream target of miR-514a-5p.…”

Polymorphisms in FCGR2A (131H/R) and FCGR2B (232I/T) are associated with the development of inhibitors in Chinese hemophilia A patients

“…In autoimmune diseases, polymorphisms in the immune response genes were reported to be related to the formation of antibody. In addition, SNPs in the regulatory regions of cytokine genes are crucial components in the pathogenesis of various diseases, including HA [21,22]. Individual immune response traits might in uence a patient's reaction to exogenous factor VIII.…”

Impacto do desenvolvimento de inibidores no tratamento e qualidade de vida de pacientes com hemofilia: uma revisão de literatura

“…Todos eles relacionados à apresentação de peptídeos de FVIII às células CD41 T-helper. Alguns polimorfismos genéticos, como os do TGF-β, da e IL10, em CD44, receptor de fator 1 estimulante de colônias (CSF1R), DOCK2, proteína MAPK9 e IQGAP2 os genes TNFalfa e CTLA4 foram sugeridos em alguns estudos como contribuintes ao risco de inibidor na hemofilia A, contudo o estudo que evidenciou essas relações envolveu poucos indivíduos (Astermark, 2015;Lai et al, 2016;Naderi et al, 2018;Zhao et al, 2019).…”