Genetic variants in Cell Adhesion Molecule 1 (CADM1): A validation study of a novel endothelial cell venous thrombosis risk factor
| Autor: | C. Y. Vossen, Stefan Boehringer, Sandra J. Hasstedt, Edwin G. Bovill, Frits R. Rosendaal, Irene D. Bezemer, Astrid van Hylckama Vlieg, Samuel Levy, Hugoline G. de Haan |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Genetic Markers Male Candidate gene Adolescent Immunoglobulins Comorbidity Polymorphism Single Nucleotide Sensitivity and Specificity Article Young Adult Risk Factors Protein C deficiency medicine Humans Genetic Predisposition to Disease Risk factor Aged Netherlands biology Cell adhesion molecule Incidence Cell Adhesion Molecule-1 Endothelial Cells Protein C Deficiency Reproducibility of Results Hematology Middle Aged medicine.disease Endothelial stem cell Venous thrombosis genetic variation Immunology biology.protein Cancer research Female venous thrombosis Antibody protein C pathway Cell Adhesion Molecules CADM1 Protein C medicine.drug |
| Zdroj: | Thrombosis Research, 134(6), 1186-1192 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2014.09.018 |
| Popis: | In a protein C deficient family, we recently identified a candidate gene, CADM1, which interacted with protein C deficiency in increasing the risk of venous thrombosis (VT). This study aimed to determine whether CADM1 variants also interact with protein C pathway abnormalities in increasing VT risk outside this family.We genotyped over 300 CADM1 variants in the population-based MEGA case-control study. We compared VT risks between cases with low protein C activity (n=194), low protein S levels (n=23), high factor VIII activity (n=165) or factor V Leiden carriers (n=580), and all 4004 controls. Positive associations were repeated in all 3496 cases and 4004 controls.We found 22 variants which were associated with VT in one of the protein C pathway risk groups. After mutual adjustment, six variants remained associated with VT. The strongest evidence was found for rs220842 and rs11608105. For rs220842, the odds ratio (OR) for VT was 3.2 (95% CI 1.2-9.0) for cases with high factor VIII activity compared with controls. In addition, this variant was associated with an increased risk of VT in the overall study population (OR: 1.5, 95% CI 1.0-2.2). The other variant, rs11608105, was not associated with VT in the overall study population (OR: 1.0, 95% CI 0.8-1.1), but showed a strong effect on VT risk (OR: 21, 95% CI 5.1-88) when combined with low protein C or S levels.In a population-based association study, we confirm a role for CADM1 variants in increasing the risk of VT by interaction with protein C pathway abnormalities. |
| Databáze: | OpenAIRE |
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