Abstract Number: PB0964
Meeting: ISTH 2021 Congress
Background: The incidence of cardiovascular diseases (CVD) is rising in Sub-Saharan Africa (SSA) due to life style changes associated with emergent urbanization. Platelets are key cells in thrombosis, hemostasis and inflammation and as such play an important role in the development of ischemic CVD such as myocardial infarction and ischemic stroke. To date, data on determinants of platelet activation and reactivity in populations in SSA is scarce.
Aims: To explore genetic and non-genetic host factors, and environmental determinants of platelet reactivity in healthy Tanzanians.
Methods: We explored genetic, non-genetic and environmental determinants of platelet reactivity in a cohort of 319 healthy Tanzanian adults. We also studied the associations of platelet parameters with circulating inflammatory markers.
Results: Genome wide association study (GWAS) showed unique set of genes associated with platelet activation/reactivity in Tanzania with little overlap with Caucasian populations. We identified 2 novel SNPs, rs903650 and rs4789332, that were associated with platelet function at the genome-wide significance threshold of p-value≤5×10-8, and confirmed polymorphisms in the PAR4 genes previously reported to increase PAR4-dependent reactivity in African descendants. Associations with inflammatory markers yielded positive correlations with plasma levels of alpha-1-antitrypsin (AAT) and negative correlations with interleukin (IL)-1β and IL-18 levels. While environmental factors had little effect on platelet reactivity, interesting associations were observed with food-derived metabolites especially with lipids. Among others, Triglyceride, Dehydrophytosphingosine and 3-methyl-4-(sulfooxy)but-2-enoic acid showed strong positive associations while 4”,5,6-Trimethylscutellarein 7-glucoside, Methyl cellulose and Mangostenone B showed strong negative associations. Clustering of subjects based on food metabolites showed significant differences in frequency of food consumption and levels of platelet activation/reactivity.
Conclusions: Platelet function in a Tanzanian population is driven by unique sets of genetic and non-genetic determinants whereby diet, through food metabolites, pose an important determinant of platelet reactivity. These differences provide novel insights in the possible health consequences of lifestyle changes in SSA.
To cite this abstract in AMA style:Kullaya V, Temba G, Fadaq N, Boahen C, Pecht T, Netea M, Mmbaga B, van der Ven A, de Mast Q. Genetic and Non-genetic Regulators of Platelet Function in Healthy Tanzanian Individuals [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/genetic-and-non-genetic-regulators-of-platelet-function-in-healthy-tanzanian-individuals/. Accessed October 1, 2023.
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