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High Levels of Complement Activating Enzyme MASP-2 Are Associated With the Risk of Future Incident Venous Thromboembolism.
Damoah, Christabel Esi; Snir, Omri; Hindberg, Kristian; Garred, Peter; Ludviksen, Judith K; Brækkan, Sigrid K; Morelli, Vânia M; Mollnes, Tom Eirik; Hansen, John-Bjarne.
Afiliação
  • Damoah CE; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.).
  • Snir O; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.).
  • Hindberg K; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.).
  • Garred P; Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark (P.G.).
  • Ludviksen JK; Research Laboratory, Nordland Hospital, Bodø, Norway (J.K.L., T.E.M.).
  • Brækkan SK; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.).
  • Morelli VM; Division of Internal Medicine, University Hospital of North Norway, Tromsø (S.K.B., V.M.M., J.-B.H.).
  • Mollnes TE; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.).
  • Hansen JB; Division of Internal Medicine, University Hospital of North Norway, Tromsø (S.K.B., V.M.M., J.-B.H.).
Arterioscler Thromb Vasc Biol ; 42(9): 1186-1197, 2022 09.
Article em En | MEDLINE | ID: mdl-35861070
BACKGROUND: Experimental studies have shown that the complement activating enzyme MASP-2 (mannose-binding lectin associated serine protease 2) exhibits a thrombin-like activity and that inhibition of MASP-2 protects against thrombosis. In this study, we investigated whether plasma MASP-2 levels were associated with risk of future venous thromboembolism (VTE) and whether genetic variants linked to MASP-2 levels were associated with VTE risk. METHODS: We conducted a population-based nested case-control study involving 410 VTE patients and 842 age- and sex-matched controls derived from the Norwegian Tromsø Study. Logistic regression was used to estimate odds ratios (ORs) of VTE across MASP-2 quartiles. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic variants associated with MASP-2 levels. A 2-sample Mendelian randomization study, also including data from the INVENT consortium (International Network of Venous Thrombosis), was performed to assess causality. RESULTS: Subjects with plasma MASP-2 in the highest quartile had a 48% higher OR of VTE (OR, 1.48 [95% CI, 1.06-2.06]) and 83% higher OR of deep vein thrombosis (OR, 1.83 [95% CI, 1.23-2.73]) compared with those with MASP-2 levels in the lowest quartile. The protein quantitative trait loci analysis revealed that 3 previously described gene variants, rs12711521 (minor allele frequency, 0.153), rs72550870 (minor allele frequency, 0.045; missense variants in the MASP2 gene), and rs2275527 (minor allele frequency, 0.220; exon variant in the adjacent MTOR gene) explained 39% of the variation of MASP-2 plasma concentration. The OR of VTE per 1 SD increase in genetically predicted MASP-2 was 1.03 ([95% CI, 1.01-1.05] P=0.0011). CONCLUSIONS: Our findings suggest that high plasma MASP-2 levels are causally associated with risk of future VTE.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose Venosa / Serina Proteases Associadas a Proteína de Ligação a Manose / Tromboembolia Venosa Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose Venosa / Serina Proteases Associadas a Proteína de Ligação a Manose / Tromboembolia Venosa Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article