Document Type : Original Article
Authors
1 Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
2 Assistant Professor, Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
3 Associate Professor, Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
Abstract
Abstract Background and Aims: Von Willebrand disease is a bleeding disorder caused by quantitative or functional defects in von Willebrand factor. The disease is found in up to 1 percent of the population. The most common symptom is mucocutaneous bleeding. Recently, studies conducted on healthy people showed that the H817Q mutation that previously known to cause von Willebrand disease was seen in the normal individuals. This study aimed to evaluate the frequency of H817Q variant of von Willebrand gene in Iranian healthy individuals.
Methods: 200 DNA samples from different Iranian ethnicities were tested. The subjects were interviewed for bleeding history and other relative symptoms. DNA was extracted from 5 ml blood samples using salting out method, following written informed consent. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the samples were genotyped by Hin1II enzyme and the results were confirmed via sequencing.
Results: The desired fragments were obtained using PCR-RFLP. One individual without any bleeding history was found to carry this allele in a heterozygote manner. The allele frequency was calculated as 0.25%.
Conclusion: The calculated allele frequency was below 1% and thereby could not be considered as a polymorphism. Von Willebrand gene contains various mutation and polymorphisms which are population specific. To understand the Iranian pattern, more studies should be done to reveal this characteristic.
Keywords
- Yee A, Kretz CA. Von Willebrand factor: form for function. Semin Thromb Hemost 2014; 40(1): 17-27.
- Springer TA. Von Willebrand factor, Jedi knight of the bloodstream. Blood 2014; 124(9): 1412-25.
- Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101(6): 2089-93.
- Shahbazi S, Mahdian R, Ala FA, Lavergne JM, Denis CV, Christophe OD. Molecular characterization of Iranian patients with type 3 von Willebrand disease. Haemophilia 2009; 15(5): 1058-64.
- James PD, Lillicrap D. von Willebrand disease: clinical and laboratory lessons learned from the large von Willebrand disease studies. Am J Hematol 2012; 87(Suppl 1): S4-11.
- Mancuso DJ, Tuley EA, Westfield LA, Lester-Mancuso TL, Le Beau MM, Sorace JM, et al. Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry 1991; 30(1): 253-69.
- Kroner PA, Foster PA, Fahs SA, Montgomery RR. The defective interaction between von Willebrand factor and factor VIII in a patient with type 1 von Willebrand disease is caused by substitution of Arg19 and His54 in mature von Willebrand factor. Blood 1996; 87(3): 1013-21.
- Rick ME, Krizek DM. Identification of a His54Gln substitution in von Willebrand factor from a patient with defective binding of factor VIII. Am J Hematol 1996; 51(4): 302-6.
- Bellissimo DB, Christopherson PA, Flood VH, Gill JC, Friedman KD, Haberichter SL, et al. VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population. Blood 2012; 119(9): 2135-40.
- Wang QY, Song J, Gibbs RA, Boerwinkle E, Dong JF, Yu FL. Characterizing polymorphisms and allelic diversity of von Willebrand factor gene in the 1000 Genomes. J Thromb Haemost 2013; 11(2): 261-9.
- Laffan MA, Lester W, O'Donnell JS, Will A, Tait RC, Goodeve A, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167(4): 453-65.
- Shahbazi S, Baniahmad F, Zakiani-Roudsari M, Raigani M, Mahdian R. Nonsense mediated decay of VWF mRNA subsequent to c.7674-7675insC mutation in type3 VWD patients. Blood Cells Mol Dis 2012; 49(1): 48-52.
- Shahbazi S, Alavi S, Mahdian R. Classification of exon 18 linked variants of VWF gene in von Willebrand disease. Int J Mol Epidemiol Genet 2012; 3(1): 77-83.
- Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Federici AB, Batlle J, et al. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost 2006; 4(4): 766-73.
- Genin E, Feingold J, Clerget-Darpoux F. Identifying modifier genes of monogenic disease: strategies and difficulties. Hum Genet 2008; 124(4): 357-68.
- Franchini M, Crestani S, Frattini F, Sissa C, Bonfanti C. ABO blood group and von Willebrand factor: biological implications. Clin Chem Lab Med 2014; 52(9): 1273-6.
)