Genetic and non-genetic drivers of platelet reactivity in healthy Tanzanian individuals.

BACKGROUD: 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.

AIM: We investigated the non-genetic 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 analysed the associations between platelet parameters with host genetic and non-genetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites.

RESULTS: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers, non-genetic 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 (SNP) genotyping identified two novel SNPs (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P <5x10), 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.

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 38029856