TY - JOUR
T1 - Differences in thrombin and plasmin generation potential between East African and Western European adults
T2 - The role of genetic and non-genetic factors
AU - Temba, Godfrey S.
AU - Vadaq, Nadira
AU - Wan, Jun
AU - Kullaya, Vesla
AU - Huskens, Dana
AU - Pecht, Tal
AU - Jaeger, Martin
AU - Boahen, Collins K.
AU - Matzaraki, Vasiliki
AU - Broeders, Wieteke
AU - Joosten, Leo A. B.
AU - Faradz, Sultana M. H.
AU - Kibiki, Gibson
AU - Middeldorp, Saskia
AU - Cavalieri, Duccio
AU - Lionetti, Paolo
AU - de Groot, Philip G.
AU - Schultze, Joachim L.
AU - Netea, Mihai G.
AU - Kumar, Vinod
AU - de Laat, Bas
AU - Mmbaga, Blandina T.
AU - van der Ven, Andre J.
AU - Roest, Mark
AU - de Mast, Quirijn
N1 - Funding Information: This study was funded by the following grants: the European Union's Horizon 2020 Research and Innovation Program under the ERA-Net Cofund action no. 727565; the Joint Programming Initiative, A Healthy Diet for a Healthy Life (JPI-HDHL; project 529051018) awarded to M.G.N., Q.d.M., A.V., D.C., P.L. and J.L.S.; ZonMw (the Netherlands Organization for Health Research and Development) awarded to M.G.N., Q.d.M. and A.V.; Radboud Revolving Research Funds (3R-Fund) awarded to G.S.T.; Indonesia Endowment Fund for Education (LPDP) given by the Ministry of Finance of the Republic of Indonesia awarded to N.V.; Non-restrictive grant (#201606130068) given by China Scholarship Council awarded to J.W; Spinoza Prize (NWO SPI94-212) and ERC Advanced grant (no. 833247) awarded to M.G.N.; and the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany's Excellence Strategy (EXC2151) 390873048 awarded to M.G.N. and J.L.S. The authors thank all volunteers in the Human Functional Genomics Studies in Tanzania and the Netherlands for their participation. We thank J. Njau and J. Kwayu for help in sample collection; H. Lemmers and H. Toenhake-Dijkstra for help in laboratory analysis; L. van de Wijer and W. van der Heijden for enrolment of the 50FG study. Funding Information: This study was funded by the following grants: the European Union's Horizon 2020 Research and Innovation Program under the ERA‐Net Cofund action no. 727565; the Joint Programming Initiative, A Healthy Diet for a Healthy Life (JPI‐HDHL; project 529051018) awarded to M.G.N., Q.d.M., A.V., D.C., P.L. and J.L.S.; ZonMw (the Netherlands Organization for Health Research and Development) awarded to M.G.N., Q.d.M. and A.V.; Radboud Revolving Research Funds (3R‐Fund) awarded to G.S.T.; Indonesia Endowment Fund for Education (LPDP) given by the Ministry of Finance of the Republic of Indonesia awarded to N.V.; Non‐restrictive grant (#201606130068) given by China Scholarship Council awarded to J.W; Spinoza Prize (NWO SPI94‐212) and ERC Advanced grant (no. 833247) awarded to M.G.N.; and the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany's Excellence Strategy (EXC2151) 390873048 awarded to M.G.N. and J.L.S. Publisher Copyright: © 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - ethnicity
KW - genetic association studies
KW - inflammation
KW - metabolome
KW - plasmin
KW - thrombin
UR - http://www.scopus.com/inward/record.url?scp=85124631612&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.15657
DO - https://doi.org/10.1111/jth.15657
M3 - Article
C2 - 35102686
SN - 1538-7933
VL - 20
SP - 1089
EP - 1105
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 5
ER -