Frequency Assessment of the H817Q (2451T→A) Variant of von Willebrand Gene in Individuals without Hemorrhagic Signs

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