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Thrombomodulin (THB...
Thrombomodulin (THBD) gene variants and thrombotic risk in a population-based cohort study
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- Manderstedt, Eric (författare)
- Kristianstad University,Faculty of Natural Science,Fakulteten för naturvetenskap
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- Halldén, Christer (författare)
- Kristianstad University,Faculty of Natural Science,Fakulteten för naturvetenskap
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- Lind-Halldén, Christina (författare)
- Kristianstad University
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- Elf, Johan (författare)
- Lund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups,Skåne University Hospital
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- Svensson, Peter J. (författare)
- Lund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups,Skåne University Hospital
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- Engström, Gunnar (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
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- Baras, Aris (författare)
- Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.
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- Lotta, Luca A. (författare)
- Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.,Regeneron Pharmaceuticals, Inc.
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- Zöller, Bengt (författare)
- Lund University,Lunds universitet,Allmänmedicin, kardiovaskulär medicin och genetik,Forskargrupper vid Lunds universitet,Family medicine, cardiovascular medicine and genetics,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
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- Elsevier BV, 2022
- 2022
- Engelska 7 s.
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 20:4, s. 929-935
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://onlinelibrar...
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https://researchport... (primary) (free)
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https://doi.org/10.1... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: The protein C anticoagulant system plays a key role in maintaining the hemostatic balance. Although several studies have identified thrombomodulin gene (THBD) variants among venous thromboembolism (VTE) patients, the role of THBD in relation to VTE in humans remains to be clarified. Objectives: This study aimed to determine the thrombotic risk of rare and common THBD variants in a large population-based cohort of middle-aged and older adults. Patients/Methods: The exome sequence of THBD was analyzed for qualifying variants in 28,794 subjects (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer study (1991–1996). Patients were followed from baseline until the first event of VTE, death, or 2018. Qualifying variants were defined as loss-of-function or non-benign (PolyPhen-2) missense variants with minor allele frequency <0.1%. Results: The single common coding variant rs1042579 was not associated with incident VTE. Sixteen rare variants were classified as qualifying and included in collapsing analysis. Seven individuals with VTE compared to 24 individuals without VTE carried one qualifying variant. Cox multivariate regression analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking and alcohol consumption, rs6025, rs1799963, and the top two eigenvectors from a principal components analysis showed a hazard ratio of 3.0 (95% confidence interval 1.4–6.3) for the rare qualifying variants. The distributions of qualifying variants in THBD showed a difference for individuals with and without incident VTE indicating a possible position effect. Conclusions: Rare qualifying THBD variants were associated with VTE, suggesting that rare variants in THBD contribute to development of VTE.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- epidemiology
- genetics
- THBD
- thrombomodulin
- venous thromboembolism
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- art (ämneskategori)
- ref (ämneskategori)
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Manderstedt, Eri ...
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Halldén, Christe ...
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Lind-Halldén, Ch ...
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Elf, Johan
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Svensson, Peter ...
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Engström, Gunnar
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Melander, Olle
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Baras, Aris
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Lotta, Luca A.
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Zöller, Bengt
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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Journal of Throm ...
- Av lärosätet
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Lunds universitet
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Högskolan Kristianstad