Immune Gene Polymorphisms Associated with Poor Response to Platelet Transfusion and Recombinant Factor VII Administration in Glanzmann Thrombasthenia

Authors: Naderi, Majid; Mirzaei, Ilia; Seidizadeh, Omid; Moud, Abolfazl Parsi; Sarani, Hosna; Avan, Amir; Taheri, Mohsen; Jahantigh, Danial; Keramati, Mohammad Reza; Sohrabi, Tayebeh

Affiliations: Zahedan Univ Med Sci, Genet Noncommunicable Dis Res Ctr, Zahedan, Iran. Zahedan Univ Med Sci, Children & Adolescents Hlth Res Ctr, Zahedan, Iran. Zahedan Univ Med Sci, Sch Med, Zahedan, Iran. Zahedan Univ Med Sci, Student Res Comm, Sch Hlth, Zahedan, Iran. Univ Milano Bicocca, Dept Biotechnol & Biosci, Milan, Italy. Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia. Mashhad Univ Med Sci, Metab Syndrome Res Ctr, Mashhad, Iran. Univ Sistan & Baluchestan, Fac Sci, Dept Biol, Zahedan, Iran. Mashhad Univ Med Sci, Canc Mol Pathol Res Ctr, Mashhad, Iran. Zahedan Univ Med Sci, Children & Adolescent Hlth Res Ctr, Dept Pediat, Zahedan, Iran. Peter Doherty Inst Infect & Immun, 792 Elizabeth St, Melbourne, Vic 3000, Australia.

Publication: Haemophilia 2024

ABSTRACT: INTRODUCTION: Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. AIMS: We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. METHODS: We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-alpha were analyzed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. RESULTS: In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-alpha rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. CONCLUSIONS: These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1 alpha, IL1-beta, IL-1R1 and IL-R antagonists might be involved in the GT progression.