Study of the Relationship between HPA-1 and HPA-5 Gene Polymorphisms and Refractory to Platelet Therapy and Recombinant Factor VII in Glanzmann Thrombasthenia Patients in Southeast of Iran
AbstractBackground: Glanzmann Thrombasthenia (GT) is a rare autosomal disease. HPA (Human Platelet Alloantigen) is a surface polymorphic alloantigen of platelets. This study was intended to investigate and compare the polymorphism of HPA-1 and HPA-5 genes in two groups of GT patients, with and without resistance to platelet and recombinant factor VII therapy.Materials and Methods: This case control study was performed on GT patients (n=16) with resistance to platelet therapy and recombinant factor VII and control group of GT patients (n=16) without resistance to platelet therapy and recombinant factor VII. The consent form was completed by each patient. Gene polymorphisms of HPA-1 and HPA-5 were investigated using SSP-PCR, and the obtained data were analyzed using statistical software SPSS16.0.Results: The results indicated no significant relationship between the studied genes and their resistance to platelet therapy and recombinant factor VII. The frequencies of HPA-1 genotype a/a were 98% and 94% in patient and control groups, respectively. The frequency of allele b was found to be less than allele a. The value of this allele was 4% in patient group and 1% in control group. In addition, the HPA-5a/a (98%) was the most frequent alloantigen?? (check it) in both groups. Seven percent (7%) of the patients had the HPA-5a/b genotype, and the HPA-5b/b was found to be absent in these individuals.Conclusion: According to the results obtained, it could be concluded that these genes play no role in resistance to platelet therapy.
Franchini M, Favaloro EJ, Lippi G. Glanzmann thrombasthenia: An update. Clin Chim Acta. 2010;411(1-2):1-6.
Bellucci S, Caen J. Molecular basis of Glanzmann’s Thrombasthenia and current strategies in treatment. Blood Rev. 2002;16(3):193-202.
Curtis, BR , McFarland JG. Human platelet antigens. 2013. Vox Sang. 2014;106(2):93-102.
Corral J, Rivera J, Gonzalez-Conejero R, et al. The number of platelet glycoprotein Ia molecules is associated with the genetically linked 807 C/T and HPA-5 polymorphisms. Transfusion. 1999. 39(4): 372-8.
Tan JY, Lian LH, Nadarajan VS. Genetic polymorphisms of human platelet antigens-1 to -6, and -15 in the Malaysian population. Blood Transfus. 2012 10(3):368-76.
Shaiegan M, Samiei S, Ataee Z, et al. Frequency of Human Platelet Antigens (HPA-2/3/5) Polymorphism in Iranians Evaluated by RFLP-PCR. IJBC; 2011;2(4):101-5.
Madani T, Samiee S, Attaei Z, et al . Platelet antigens frequency in blood donors: comparison of molecular detection with ELISA method (for HPA-1a) . SJIBTO. 2007; 4(3): 165-174.
Tanboğa İH, Can MM, Özkan A, et al. Relationship between human platelet antigen-1 gene polymorphism and clopidogrel resistance in patients with coronary artery disease.Turk Kardiyol Dern Ars. 2013;41(5):379-85.
Soundravally R, Hoti SL. Immunopathogenesis of dengue hemorrhagic fever and shock syndrome: Role of TAP and HPA gene polymorphism. Hum Immunol. 2007; 68(12):973-9.
Ferrer G, Muñiz-Diaz E, Aluja M, et al. Analysis of human platelet antigen systems in a Moroccan Berber populaion. Transfus Med. 2002;12(1):49-54.
Drzewek K, Brojer E, Zupanska B. The frequency of human platelet antigen (HPA) genotypes in the Polish population. Transfus Med. 1998;8(4):339-42.
Poon MC, Zotz R, Di Minno G, et al. Glanzmann’s thrombasthenia Treatment: A Prospective Observational Registry on the Use of Recombinant Human Activated factor VII and other hemostatic Agents. Semin Hematol.2006; 43(1 Suppl 1):S33-6.