Selectin haplotypes and the risk of venous thrombosis: influence of linkage disequilibrium with the factor V Leiden mutation
| Autor: | F. R. Rosendaal, R M Bertina, S. Uitte De Willige, M. de Visser, H. L. Vos, Jeanine J. Houwing-Duistermaat |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Risk Linkage disequilibrium Adolescent Recombination hotspot Disease Biology Thrombophilia Linkage Disequilibrium medicine Humans Platelet Aged Venous Thrombosis Polymorphism Genetic Models Genetic Haplotype Factor V Thrombosis Hematology Middle Aged medicine.disease Venous thrombosis Haplotypes Mutation Immunology Female Selectin |
| Zdroj: | Journal of Thrombosis and Haemostasis. 6:478-485 |
| ISSN: | 1538-7836 |
| DOI: | 10.1111/j.1538-7836.2007.02879.x |
| Popis: | Summary. Background: Selectins (E-, L- and P-selectin) and their most important counter-receptor P-selectin glycoprotein ligand (SELPLG) facilitate the interaction of platelets, leukocytes and endothelial cells at inflammatory sites. Selectin polymorphisms/haplotypes have been associated with cardiovascular disease. Objectives: We investigated the association between haplotypes (H) of these four genes and deep venous thrombosis (DVT) risk. We additionally explored the effect of linkage disequilibrium (LD) with the nearby Factor V Leiden mutation (FVL). Furthermore, interactions between SELPLG polymorphisms and selectin polymorphisms were investigated. Patients/methods: Leiden Thrombophilia Study (LETS) subjects were genotyped for 24 polymorphisms by TaqMan or PCR–RFLP, detecting all common haplotypes in four blocks. P-selectin was analyzed in two blocks, upstream (SELPup) and downstream (SELPdown) of the recombination hotspot. Results: In E- and L-selectin, none of the haplotypes was associated with DVT risk. In SELPup, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0–1.7), whereas H4-carriers had a 1.4-fold decreased risk (95% CI, 0.5–1.0). In SELPdown, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0–1.7). Because of LD with FVL, we subsequently excluded all FVL-carriers and all risks disappeared. Mutual adjustment within a logistic regression model resulted in disappearance of the risks for the SELP haplotypes, whereas FVL risk remained. Conclusions: After adjustment for LD with FVL, none of the selectin haplotypes was associated with DVT risk, showing that the increased risks of the selectin haplotypes were a reflection of the effect of FVL on thrombosis risk. |
| Databáze: | OpenAIRE |
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