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Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients
Kristianstad University, Plattformen för molekylär analys. Kristianstad University, Faculty of Natural Science, Avdelningen för miljö- och biovetenskap.
Kristianstad University, Forskningsmiljön Biomedicin. Kristianstad University, Faculty of Natural Science, Avdelningen för miljö- och biovetenskap.
Danmark & Lund University.
Kristianstad University, Forskningsmiljön Biomedicin. Kristianstad University, Faculty of Natural Science, Avdelningen för miljö- och biovetenskap.ORCID iD: 0000-0002-9355-3901
2018 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 2Article in journal (Refereed) Published
Abstract [en]

von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. This study aims to screen comprehensively for CLEC4M variants and investigate their association with type 1 VWD in the Swedish population. In order to screen for CLEC4M variants, the CLEC4M gene region was re-sequenced and the polymorphic neck region was genotyped in 106 type 1 VWD patients from unrelated type 1 VWD families. Single nucleotide variants (SNV) and variable number tandem repeat (VNTR) allele and genotype frequencies were then compared with 294 individuals from the 1000Genomes project and 436 Swedish control individuals. Re-sequencing identified a total of 42 SNVs. Rare variants showed no accumulation in type 1 VWD patients and are not thought to contribute substantially to type 1 VWD. The only missense mutation (rs2277998, NP_001138379.1:p.Asp224Asn) had a higher frequency in type 1 VWD patients than in controls (4.9%). The VNTR genotypes 57 and 67 were observed at higher frequencies than expected in type 1 VWD patients (6.4% and 6.2%) and showed an increase in patients compared with controls (7.4% and 3.1%). Strong linkage disequilibrium in the CLEC4M region makes it difficult to distinguish between the effect of the missense mutation and the VNTR genotypes. In conclusion, heterozygous VNTR genotypes 57 and 67 of CLEC4M were highly enriched and are the most likely mechanism through which CLEC4M contributes to disease in the Swedish type 1 VWD population.

Place, publisher, year, edition, pages
2018. Vol. 13, no 2
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:hkr:diva-17855DOI: 10.1371/journal.pone.0192024ISI: 000423793400052PubMedID: 29389944OAI: oai:DiVA.org:hkr-17855DiVA, id: diva2:1180922
Available from: 2018-02-07 Created: 2018-02-07 Last updated: 2021-06-14Bibliographically approved

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