TY  - JOUR
TI  - Effect of CTLA-4 and TNF-α Gene Polymorphisms on Inhibitor Development in a Turkish Cohort of Severe Hemophilia A Cases with Intron 22 Inversion Mutation: An Analytical Study
AB  - Objective: The development of neutralizing antibodies against in- fused factor VIII called inhibitor is the most challenging treatment complication in hemophilia A (HA) p atients. Associated factors for inhibitor development are classified into 2 groups (genetics and non-genetics). Genetic factors other than mu- tation type of F8 gene include family history, ethnical origin, human leucocyte anti- gen 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- α)] 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- α (c.-308G>A; rs1800629) using Sanger sequencing in both groups. Results: In this study, no sig- nificant 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-α 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 as- sociated with the inhibitor development, whereas c.-308G>A variant in TNF-α, the A allele is related to the risk of inhibitor development.
AU  - ozbek, namik yasar
AU  - Akgun, Bilcag
AU  - Mehdiyeva, Humay
AU  - Onay, Huseyin
AU  - isik, esra
AU  - Durmuş Özen, Başak
AU  - Ozkinay, Ferda
AU  - ALPAY, ARAZ
AU  - sezgin evim, melike
AU  - Kavakli, Kaan
AU  - köse, melis
AU  - ATIK, TAHIR
DO  - 10.5336/medsci.2021-86664
PY  - 2022
JO  - Türkiye Klinikleri Tıp Bilimleri Dergisi
VL  - 42
IS  - 3
SN  - 1300-0292
SP  - 159
EP  - 163
DB  - TRDizin
UR  - http://search/yayin/detay/1135079
ER  -