New associations: <i><scp>INFG</scp></i> and <i><scp>TGFB</scp>1</i> genes and the inhibitor development in severe haemophilia A

Alencar, Josiane Bazzo de; Macedo, Luciana Conci; Barros, Morgana Ferreira de; Rodrigues, Camila; Shinzato, Andressa Higa; Pelissari, C. B.; Machado, J. C.; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

doi:10.1111/hae.12685

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…As known, cytokines are more or less directly involved in the antibody-mediated immune responses [26,27]. In patients with autoimmune disease, polymorphisms in the immune response genes were found to be associated with antibody formation.…”

Section: Discussionmentioning

confidence: 99%

“…The development of FVIII inhibitor is the main complication of replacement therapy in patients with haemophilia A. Indeed, the immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form [26]. For instance, polymorphic variants at IL-2 gene was associated with several autoimmune conditions including type 1 diabetes, rheumatoid arthritis, multiple sclerosis and bleeding disorders [16].…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β and IL-2 cytokines were associated with susceptibility to various diseases including cancers, cardiac diseases, inflammatory diseases, bleeding disorders and others. To date, several single nucleotide polymorphisms (SNPs) have been shown to affect TGF-β (rs1982037) and IL-2 (rs2069762, rs4833248) expression and could therefore be used as susceptibility biomarkers [16][17][18][19][20][21][22][23][24][25][26]. The aim of this study was to investigate the association between polymorphic variants of the IL-2 and TGF-β genes, and development of FVIII inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the TGF-β1 (rs1982037) and IL-2 (rs2069762, rs4833248) genes are not associated with inhibitor development in Iranian patients with hemophilia A

et al. 2018

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Objectives Development of neutralizing antibodies against factor VIII is the major complication in hemophilia care which makes replacement therapies ineffective. The reports showed that inflammatory cytokines play an important role in inhibitor production. In the present study, the relationship between inhibitor development and the polymorphisms of two cytokine genes was studied in severe hemophiliac patients from Iran. Methods In this case-control study, three polymorphisms of immune regulatory genes [TGF-β (rs1982037) and IL-2 (rs2069762, rs4833248)] were analyzed in 100 Iranian hemophilia A patients divided into 55 inhibitor positive and 45 inhibitor negative patients using Tetra primer ARMS PCR, and DNA sequencing. Results The analysis of polymorphisms in the TGF-β and IL-2 genes showed no association between the genotypes and the production of inhibitors (p> 0.05). Also, comparison of allele frequencies for TGF-β and IL-2 genes between two groups indicated no significant differences associated with the development of FVIII inhibitors (p > 0.05). Discussion In contrast with some reports involving the correlation between polymorphisms of the TGF-β1 and IL-2 genes and inhibitor development in the world, no statistically significant differences in analysis of the alleles and genotypes for TGF-β and IL-2 genes were found between the inhibitor and non-inhibitor Iranian patients. Thus, other genetic markers influencing the immune response to replacement therapy in patients with hemophilia should be identified. Conclusions Regarding our results in molecular predisposition for inhibitor development, further studies of effective genetic markers are required as a prerequisite for the development of novel immunogenic therapeutic approaches in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the TGF-β1 (rs1982037) and IL-2 (rs2069762, rs4833248) genes are not associated with inhibitor development in Iranian patients with hemophilia A

et al. 2018

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“…Many genes that play an important role in the antibody‐mediated immune response may affect FVIII inhibitor production . Polymorphisms in immune response‐related genes have been suggested in various studies and cohorts as important genetic risk factors for inhibitor formation . Some gene polymorphisms, such as those in the IL10, TNFa and CTLA4 genes, have been suggested as contributing determinants of inhibitor risk .…”

Section: Introductionmentioning

confidence: 99%

“…5 Polymorphisms in immune response-related genes have been suggested in various studies and cohorts as important genetic risk factors for inhibitor formation. [6][7][8] Some gene polymorphisms, such as those in the IL10, TNFa and CTLA4 genes, have been suggested as contributing determinants of inhibitor risk. [9][10][11] Lu et al 12 found that a haplotype of IL10 was associated with inhibitor risk in Chinese HA patients.…”

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confidence: 99%

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

Zhao

Zhang

Liu

et al. 2019

Int J Lab Hematology

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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.

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Effect of IFN-γ +874 T/A polymorphism on clinical manifestations of dengue: a meta-analysis

Kaur¹,

Gupta²,

Singh³

et al. 2021

J Genet

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New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A

Abstract: This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII.

Cited by 9 publications

References 25 publications

Polymorphisms in the TGF-β1 (rs1982037) and IL-2 (rs2069762, rs4833248) genes are not associated with inhibitor development in Iranian patients with hemophilia A

Polymorphisms in the TGF-β1 (rs1982037) and IL-2 (rs2069762, rs4833248) genes are not associated with inhibitor development in Iranian patients with hemophilia A

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

Effect of IFN-γ +874 T/A polymorphism on clinical manifestations of dengue: a meta-analysis

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