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Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors

BACKGROUND: Geographic variability in coagulation across populations and their determinants are poorly understood. OBJECTIVE: To compare thrombin (TG) and plasmin (PG) generation parameters between healthy Tanzanian and Dutch individuals, and to study associations with inflammation and different gen...

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Autores principales: Temba, Godfrey S., Vadaq, Nadira, Wan, Jun, Kullaya, Vesla, Huskens, Dana, Pecht, Tal, Jaeger, Martin, Boahen, Collins K., Matzaraki, Vasiliki, Broeders, Wieteke, Joosten, Leo A. B., Faradz, Sultana M. H., Kibiki, Gibson, Middeldorp, Saskia, Cavalieri, Duccio, Lionetti, Paolo, de Groot, Philip G., Schultze, Joachim L., Netea, Mihai G., Kumar, Vinod, de Laat, Bas, Mmbaga, Blandina T., van der Ven, Andre J., Roest, Mark, de Mast, Quirijn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305795/
https://www.ncbi.nlm.nih.gov/pubmed/35102686
http://dx.doi.org/10.1111/jth.15657
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author Temba, Godfrey S.
Vadaq, Nadira
Wan, Jun
Kullaya, Vesla
Huskens, Dana
Pecht, Tal
Jaeger, Martin
Boahen, Collins K.
Matzaraki, Vasiliki
Broeders, Wieteke
Joosten, Leo A. B.
Faradz, Sultana M. H.
Kibiki, Gibson
Middeldorp, Saskia
Cavalieri, Duccio
Lionetti, Paolo
de Groot, Philip G.
Schultze, Joachim L.
Netea, Mihai G.
Kumar, Vinod
de Laat, Bas
Mmbaga, Blandina T.
van der Ven, Andre J.
Roest, Mark
de Mast, Quirijn
author_facet Temba, Godfrey S.
Vadaq, Nadira
Wan, Jun
Kullaya, Vesla
Huskens, Dana
Pecht, Tal
Jaeger, Martin
Boahen, Collins K.
Matzaraki, Vasiliki
Broeders, Wieteke
Joosten, Leo A. B.
Faradz, Sultana M. H.
Kibiki, Gibson
Middeldorp, Saskia
Cavalieri, Duccio
Lionetti, Paolo
de Groot, Philip G.
Schultze, Joachim L.
Netea, Mihai G.
Kumar, Vinod
de Laat, Bas
Mmbaga, Blandina T.
van der Ven, Andre J.
Roest, Mark
de Mast, Quirijn
author_sort Temba, Godfrey S.
collection PubMed
description BACKGROUND: Geographic variability in coagulation across populations and their determinants are poorly understood. OBJECTIVE: To compare thrombin (TG) and plasmin (PG) generation parameters between healthy Tanzanian and Dutch individuals, and to study associations with inflammation and different genetic, host and environmental factors. METHODS: TG and PG parameters were measured in 313 Tanzanians of African descent living in Tanzania and 392 Dutch of European descent living in the Netherlands and related to results of a dietary questionnaire, circulating inflammatory markers, genotyping, and plasma metabolomics. RESULTS: Tanzanians exhibited an enhanced TG and PG capacity, compared to Dutch participants. A higher proportion of Tanzanians had a TG value in the upper quartile with a PG value in the lower/middle quartile, suggesting a relative pro‐coagulant state. Tanzanians also displayed an increased normalized thrombomodulin sensitivity ratio, suggesting reduced sensitivity to protein C. In Tanzanians, PG parameters (lag time and TTP) were associated with seasonality and food‐derived plasma metabolites. The Tanzanians had higher concentrations of pro‐inflammatory cytokines, which correlated strongly with TG and PG parameters. There was limited overlap in genetic variation associated with TG and PG parameters between the two cohorts. Pathway analysis of genetic variants in the Tanzanian cohort revealed multiple immune pathways that were enriched with TG and PG traits, confirming the importance of co‐regulation between coagulation and inflammation. CONCLUSIONS: Tanzanians have an enhanced TG and PG potential compared to Dutch individuals, which may relate to differences in inflammation, genetics and diet. These observations highlight the importance of better understanding of the geographic variability in coagulation across populations.
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spelling pubmed-93057952022-07-28 Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors Temba, Godfrey S. Vadaq, Nadira Wan, Jun Kullaya, Vesla Huskens, Dana Pecht, Tal Jaeger, Martin Boahen, Collins K. Matzaraki, Vasiliki Broeders, Wieteke Joosten, Leo A. B. Faradz, Sultana M. H. Kibiki, Gibson Middeldorp, Saskia Cavalieri, Duccio Lionetti, Paolo de Groot, Philip G. Schultze, Joachim L. Netea, Mihai G. Kumar, Vinod de Laat, Bas Mmbaga, Blandina T. van der Ven, Andre J. Roest, Mark de Mast, Quirijn J Thromb Haemost HAEMOSTASIS BACKGROUND: Geographic variability in coagulation across populations and their determinants are poorly understood. OBJECTIVE: To compare thrombin (TG) and plasmin (PG) generation parameters between healthy Tanzanian and Dutch individuals, and to study associations with inflammation and different genetic, host and environmental factors. METHODS: TG and PG parameters were measured in 313 Tanzanians of African descent living in Tanzania and 392 Dutch of European descent living in the Netherlands and related to results of a dietary questionnaire, circulating inflammatory markers, genotyping, and plasma metabolomics. RESULTS: Tanzanians exhibited an enhanced TG and PG capacity, compared to Dutch participants. A higher proportion of Tanzanians had a TG value in the upper quartile with a PG value in the lower/middle quartile, suggesting a relative pro‐coagulant state. Tanzanians also displayed an increased normalized thrombomodulin sensitivity ratio, suggesting reduced sensitivity to protein C. In Tanzanians, PG parameters (lag time and TTP) were associated with seasonality and food‐derived plasma metabolites. The Tanzanians had higher concentrations of pro‐inflammatory cytokines, which correlated strongly with TG and PG parameters. There was limited overlap in genetic variation associated with TG and PG parameters between the two cohorts. Pathway analysis of genetic variants in the Tanzanian cohort revealed multiple immune pathways that were enriched with TG and PG traits, confirming the importance of co‐regulation between coagulation and inflammation. CONCLUSIONS: Tanzanians have an enhanced TG and PG potential compared to Dutch individuals, which may relate to differences in inflammation, genetics and diet. These observations highlight the importance of better understanding of the geographic variability in coagulation across populations. John Wiley and Sons Inc. 2022-02-10 2022-05 /pmc/articles/PMC9305795/ /pubmed/35102686 http://dx.doi.org/10.1111/jth.15657 Text en © 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle HAEMOSTASIS
Temba, Godfrey S.
Vadaq, Nadira
Wan, Jun
Kullaya, Vesla
Huskens, Dana
Pecht, Tal
Jaeger, Martin
Boahen, Collins K.
Matzaraki, Vasiliki
Broeders, Wieteke
Joosten, Leo A. B.
Faradz, Sultana M. H.
Kibiki, Gibson
Middeldorp, Saskia
Cavalieri, Duccio
Lionetti, Paolo
de Groot, Philip G.
Schultze, Joachim L.
Netea, Mihai G.
Kumar, Vinod
de Laat, Bas
Mmbaga, Blandina T.
van der Ven, Andre J.
Roest, Mark
de Mast, Quirijn
Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title_full Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title_fullStr Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title_full_unstemmed Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title_short Differences in thrombin and plasmin generation potential between East African and Western European adults: The role of genetic and non‐genetic factors
title_sort differences in thrombin and plasmin generation potential between east african and western european adults: the role of genetic and non‐genetic factors
topic HAEMOSTASIS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305795/
https://www.ncbi.nlm.nih.gov/pubmed/35102686
http://dx.doi.org/10.1111/jth.15657
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