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  • Manderstedt, EricKristianstad University,Faculty of Natural Science,Fakulteten för naturvetenskap (author)

Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults : A Population-Based Cohort Study

  • Article/chapterEnglish2022

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  • Wiley-Blackwell Publishing Ltd,2022

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  • LIBRIS-ID:oai:lup.lub.lu.se:41e2154d-17b8-4cbc-bc2d-ad78f687ad5a
  • https://lup.lub.lu.se/record/41e2154d-17b8-4cbc-bc2d-ad78f687ad5aURI
  • https://doi.org/10.1161/JAHA.121.023018DOI
  • oai:researchportal.hkr.se/admin:publications/39d8743c-6bb3-4e75-bee9-b2022fe22adcURI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Publisher Copyright: © 2022 The Authors and Regeneron Genetics Center. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creat​ive Commo​ns Attri​bution-NonCo​mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  • BACKGROUND: Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. METHODS AND RESULTS: Factor V Leiden, prothrombin G20210A and protein-coding variants in the PROC (protein C), PROS1 (protein S), and SERPINC1 (antithrombin) anticoagulant genes were determined in 29 387 subjects (born 1923–1950, 60% women) who participated in the Malmö Diet and Cancer study (1991–1996). The Human Gene Mutation Database was used to define 68 disease-causing mutations. Patients were followed up from baseline until the first event of venous thromboembolism (VTE), death, or Dec 31, 2018. Carriership (n=908, 3.1%) for disease-causing mutations in the PROC, PROS1, and SERPINC1 genes was associated with incident VTE: Hazard ratio (HR) was 1.6 (95% CI, 1.3–1.9). Variants not in Human Gene Mutation Database were not linked to VTE (HR, 1.1; 95% CI, 0.8–1.5). Heterozygosity for rs6025 and rs1799963 was associated with incident VTE: HR, 1.8 (95% CI, 1.6–2.0) and HR, 1.6 (95% CI, 1.3–2.0), respectively. The HR for carrying 1 classical thrombophilia variant was 1.7 (95% CI, 1.6–1.9). HR was 3.9 (95% CI, 3.1–5.0) for carriers of ≥2 thrombophilia variants. CONCLUSIONS: The 5 classic thrombophilias are associated with a dose-graded risk of VTE in middle-aged and older adults. Disease-causing variants in the PROC, PROS1, and SERPINC1 genes were more common than the rs1799963 variant but the conferred genetic risk was comparable with the rs6025 and rs1799963 variants.

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  • Lind-Halldén, ChristinaKristianstad University,Faculty of Natural Science,Fakulteten för naturvetenskap(Swepub:lu)klke-cha (author)
  • Halldén, ChristerKristianstad University(Swepub:lu)klke-cha (author)
  • Elf, JohanLund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups(Swepub:lu)med-jne (author)
  • Svensson, Peter J.Lund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups(Swepub:lu)medf-psv (author)
  • Dahlbäck, BjörnLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-bda (author)
  • Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)smi-gen (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
  • Baras, ArisRegeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc. (author)
  • Lotta, Luca A.Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc. (author)
  • Zöller, BengtLund University,Lunds universitet,Allmänmedicin, kardiovaskulär medicin och genetik,Forskargrupper vid Lunds universitet,Family medicine, cardiovascular medicine and genetics,Lund University Research Groups,Region Skåne(Swepub:lu)medf-bzo (author)
  • Kristianstad UniversityFaculty of Natural Science (creator_code:org_t)
  • Regeneron Genetics Center

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  • In:Journal of the American Heart Association: Wiley-Blackwell Publishing Ltd11:42047-9980

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