Risk prediction of developing venous thrombosis in combined oral contraceptive users
| Autor: | Goranka Tanackovic, Thierry Daniel Pache, Pierre Suchon, Valérie Buchillier, Zoltán Kutalik, Maude Muriset, Joëlle Michaud, Aaron McDaid, Emmanuelle Logette |
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| Přispěvatelé: | Institute of Social and Preventive Medicine, Lausanne university hospital, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), EPFL Innovation Park, Gene Predictis SA, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lausanne University Hospital, Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Swiss Institute of Bioinformatics |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
variabilité génétique
lcsh:Medicine 030204 cardiovascular system & hematology Cardiovascular Medicine SUSCEPTIBILITY VARIANTS Vascular Medicine 0302 clinical medicine Risk Factors genetic variability Medicine and Health Sciences Young adult lcsh:Science birth control ASSOCIATION THROMBOEMBOLISM MIGRAINE GENETICS UPDATE education.field_of_study Multidisciplinary Obstetrics and Gynecology risk assessment Hematology Venous Thromboembolism Middle Aged 3. Good health Deep Vein Thrombosis Venous thrombosis Contraceptives Oral Combined facteur de risque risk factor contraception Cardiovascular Diseases Area Under Curve Medical genetics Female venous thrombosis Risk assessment Research Article Adult medicine.medical_specialty Genotyping Adolescent Population Médecine humaine et pathologie Research and Analysis Methods 03 medical and health sciences Young Adult Internal medicine Factor V Leiden medicine Humans Female Contraception Genetic variability Risk factor education Molecular Biology Techniques Blood Coagulation Molecular Biology Clinical Genetics Evolutionary Biology Coagulation Disorders Population Biology business.industry lcsh:R Biology and Life Sciences Thrombosis Human Genetics medicine.disease Surgery ROC Curve Women's Health lcsh:Q Human health and pathology business évaluation des risques 030217 neurology & neurosurgery Population Genetics [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology thrombose veineuse |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2017, 12 (7), ⟨10.1371/journal.pone.0182041⟩ Plos One 7 (12), . (2017) PloS one, vol. 12, no. 7, pp. e0182041 PLoS ONE, Vol 12, Iss 7, p e0182041 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0182041⟩ |
| Popis: | Background Venous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by 3 to 7 fold, depending on estrogen dosage and the type of progestin present in the pill. One out of 1'000 women using CC develops thrombosis, often with life-long consequences; a risk assessment is therefore necessary prior to such treatment. Currently known clinical risk factors associated with VTE development in general are routinely checked by medical doctors, however they are far from being sufficient for risk prediction, even when combined with genetic tests for Factor V Leiden and Factor II G20210A variants. Thus, clinical and notably genetic risk factors specific to the development of thrombosis associated with the use of CC in particular should be identified. Methods and findings Step-wise (logistic) model selection was applied to a population of 1622 women using CC, half of whom (794) had developed a thromboembolic event while using contraceptives. 46 polymorphisms and clinical parameters were tested in the model selection and a specific combination of 4 clinical risk factors and 9 polymorphisms were identified. Among the 9 polymorphisms, there are two novel genetic polymorphisms (rs1799853 and rs4379368) that had not been previously associated with the development of thromboembolic event. This new prediction model outperforms (AUC 0.71, 95% CI 0.69-0.74) previously published models for general thromboembolic events in a cross-validation setting. Further validation in independent populations should be envisaged. Conclusion We identified two new genetic variants associated to VTE development, as well as a robust prediction model to assess the risk of thrombosis for women using combined oral contraceptives. This model outperforms current medical practice as well as previously published models and is the first model specific to CC use. |
| Databáze: | OpenAIRE |
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