Genetic and nongenetic drivers of platelet reactivity in healthy Tanzanian individuals
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
BACKGROUND: Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown.
OBJECTIVES: We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania.
METHODS: Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites.
RESULTS: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10-8) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity.
CONCLUSION: Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Journal of thrombosis and haemostasis : JTH - 22(2024), 3 vom: 29. März, Seite 805-817 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kullaya, Vesla I [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Genetics |
|---|
| Anmerkungen: |
Date Completed 01.03.2024 Date Revised 01.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jtha.2023.11.014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365209988 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365209988 | ||
| 003 | DE-627 | ||
| 005 | 20240301232152.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jtha.2023.11.014 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1313.xml |
| 035 | |a (DE-627)NLM365209988 | ||
| 035 | |a (NLM)38029856 | ||
| 035 | |a (PII)S1538-7836(23)00852-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kullaya, Vesla I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic and nongenetic drivers of platelet reactivity in healthy Tanzanian individuals |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.03.2024 | ||
| 500 | |a Date Revised 01.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown | ||
| 520 | |a OBJECTIVES: We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania | ||
| 520 | |a METHODS: Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites | ||
| 520 | |a RESULTS: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10-8) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity | ||
| 520 | |a CONCLUSION: Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a P-selectin | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a platelet activation | |
| 650 | 4 | |a platelets | |
| 650 | 4 | |a protease-activated receptors | |
| 650 | 7 | |a Receptor, PAR-1 |2 NLM | |
| 700 | 1 | |a Temba, Godfrey S |e verfasserin |4 aut | |
| 700 | 1 | |a Vadaq, Nadira |e verfasserin |4 aut | |
| 700 | 1 | |a Njau, Judith |e verfasserin |4 aut | |
| 700 | 1 | |a Boahen, Collins K |e verfasserin |4 aut | |
| 700 | 1 | |a Nkambule, Bongani B |e verfasserin |4 aut | |
| 700 | 1 | |a Thibord, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ming-Huei |e verfasserin |4 aut | |
| 700 | 1 | |a Pecht, Tal |e verfasserin |4 aut | |
| 700 | 1 | |a Lyamuya, Furaha |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Vinod |e verfasserin |4 aut | |
| 700 | 1 | |a Netea, Mihai G |e verfasserin |4 aut | |
| 700 | 1 | |a Mmbaga, Blandina T |e verfasserin |4 aut | |
| 700 | 1 | |a van der Ven, Andre |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Andrew D |e verfasserin |4 aut | |
| 700 | 1 | |a de Mast, Quirijn |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of thrombosis and haemostasis : JTH |d 2003 |g 22(2024), 3 vom: 29. März, Seite 805-817 |w (DE-627)NLM126285683 |x 1538-7836 |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:3 |g day:29 |g month:03 |g pages:805-817 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jtha.2023.11.014 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 3 |b 29 |c 03 |h 805-817 | ||