Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients.
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 w...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5794141?pdf=render |
| _version_ | 1811201398637854720 |
|---|---|
| author | Eric Manderstedt Christina Lind-Halldén Stefan Lethagen Christer Halldén |
| author_facet | Eric Manderstedt Christina Lind-Halldén Stefan Lethagen Christer Halldén |
| author_sort | Eric Manderstedt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:21:16Z |
| format | Article |
| id | doaj.art-812583975df54516b855f618980ff53b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T02:21:16Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-812583975df54516b855f618980ff53b2022-12-22T03:52:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01132e019202410.1371/journal.pone.0192024Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients.Eric ManderstedtChristina Lind-HalldénStefan LethagenChrister Halldénvon 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.http://europepmc.org/articles/PMC5794141?pdf=render |
| spellingShingle | Eric Manderstedt Christina Lind-Halldén Stefan Lethagen Christer Halldén Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. PLoS ONE |
| title | Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. |
| title_full | Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. |
| title_fullStr | Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. |
| title_full_unstemmed | Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. |
| title_short | Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients. |
| title_sort | genetic variation in the c type lectin receptor clec4m in type 1 von willebrand disease patients |
| url | http://europepmc.org/articles/PMC5794141?pdf=render |
| work_keys_str_mv | AT ericmanderstedt geneticvariationinthectypelectinreceptorclec4mintype1vonwillebranddiseasepatients AT christinalindhallden geneticvariationinthectypelectinreceptorclec4mintype1vonwillebranddiseasepatients AT stefanlethagen geneticvariationinthectypelectinreceptorclec4mintype1vonwillebranddiseasepatients AT christerhallden geneticvariationinthectypelectinreceptorclec4mintype1vonwillebranddiseasepatients |