Effect of CTLA-4 and TNF-? Gene Polymorphisms on Inhibitor Development in a Turkish Cohort of Severe Hemophilia A Cases with Intron 22 Inversion Mutation: An Analytical Study
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Turkiye Klinikleri
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Objective: The development of neutralizing antibodies against in-fused factor VIII called inhibitor is the most challenging treatment complication in hemophilia A (HA) patients. Associated factors for inhibitor development are classified into 2 groups (genetics and non-genetics). Genetic factors other than mutation type of F8 gene include family history, ethnical origin, human leucocyte antigen haplotype, and a number of polymorphisms in genes which play role in immune system. In this study, we aimed to analyze the association between 3 variants in 2 genes [c.-318C>T; rs5742909 and c.49A>G; rs231775 in CTLA-4 and c.-308G>A; rs1800629 in tumor necrosis factor alpha (TNF-?)] and inhibitor development in a cohort of severe HA patients with intron 22 inversion (inv22) mutation. Material and Methods: The study included in 94 severe HA patients with inv22. Two groups were established according to the inhibitor status: inhibitor positive and inhibitor negative. We investigated 2 single nucleotide polymorphisms in CTLA-4 (c.-318C>T; rs5742909 and c.49A>G; rs231775) and one in TNF-? (c.-308G>A; rs1800629) using Sanger sequencing in both groups. Results: In this study, no significant relationship between CTLA-4 polymorphisms and inhibitor development was observed in severe HA patients with inv22 mutation. However, the A allele for c.-308G>A variant in TNF-? was found to be associated with the increased risk for inhibitor development in those patients. Conclusion: In Turkish severe HA patients with inv22 mutation, c.-318C>T and c.49A>G variants in CTLA-4 gene are not associated with the inhibitor development, whereas c.-308G>A variant in TNF-?, the A allele is related to the risk of inhibitor development. © 2022 by Türkiye Klinikleri.
Açıklama
Anahtar Kelimeler
CTLA-4, Hemophilia, inhibitor, intron 22 inversion, TNF-?, blood clotting factor 8, cytotoxic T lymphocyte antigen 4, Inversion Mutation, leukocyte antigen, neutralizing antibody, transforming growth factor beta1, tumor necrosis factor, unclassified drug, allele, Article, cohort analysis, DNA polymorphism, gene frequency, gene mutation, gene rearrangement, genetic risk, genetic susceptibility, genotype, haplotype, hemophilia, high throughput sequencing, human, intron, inversion mutation, major clinical study, polymerase chain reaction, prevalence, questionnaire, risk factor, Sanger sequencing, single nucleotide polymorphism
Kaynak
Turkiye Klinikleri Journal of Medical Sciences
WoS Q Değeri
Scopus Q Değeri
Q4
Cilt
42
Sayı
3
