A common VWF exon 28 haplotype in the Turkish population

Abstract

An increasing number of mutations and polymorphisms have been identified in the von Willebrand factor (VWF) gene of patients with von Willebrand disease (VWD). Most of the sequence alterations are within exon 28, duplicated in the VWF pseudogene on chromosome 22. Genetic recombination causing the gene conversion between the VWF gene and its pseudogene is associated with multiple substitutions in the VWF gene and with VWD. In the present study, VWF gene exon 28 was analyzed in 33 patients with VWD by DNA sequencing. A total of 73% of the patients were heterozygous for p.D1472H, p.V1485L, p.1500A, p.1501F, p.L1503P, and p.S1506L single-nucleotide polymorphisms. Family analysis revealed that the gene conversion occurred between the VWF gene and its pseudogene in 3 patients. Case-control association analysis by Haploview 4.2 did not show an association between the haplotype and VWD. In conclusion, a common exon 28 haplotype in the Turkish population, which might have arisen from the gene conversion events in the founder population, was identified.

Keywords: VWD; VWF; VWF exon 28; VWF gene conversion; VWF haplotype.