İntron 22 Mutasyon Taşıyıcısı Ağır Hemofili A Hastalarında CTLA-4 ve TNF-? Gen Polimorfizmlerinin İnhibitör Gelişimi Üzerine Etkisi: Analitik Bir Araştırma
| Autor: | Mehdiyeva H., Işik E., Köse M., Akgün B., Durmuş B., Alpay A., Kavakli K. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
haplotype
Sanger sequencing intron tumor necrosis factor genotype polymerase chain reaction prevalence gene rearrangement transforming growth factor beta1 Inversion Mutation gene frequency genetic risk Article high throughput sequencing single nucleotide polymorphism hemophilia gene mutation human leukocyte antigen cytotoxic T lymphocyte antigen 4 questionnaire TNF-? allele neutralizing antibody intron 22 inversion cohort analysis major clinical study unclassified drug inhibitor risk factor blood clotting factor 8 DNA polymorphism CTLA-4 genetic susceptibility |
| Popis: | 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. Ege Üniversitesi This study was approved way the Ege University Scientific Research Projects Coordination (Grant Number 20176) and supported by Ege University Research Fund. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|