# PUFAs and gene variation affecting aspirin antiplatelet response

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2020 · $691,629

## Abstract

ABSTRACT – Project 3
The idea that dietary ω3 polyunsaturated fatty acids (ω3 PUFAs), which are high in fish oils and other marine
diet constituents, have cardioprotective and other beneficial health properties has captured the attention of the
scientific community for more than a generation. Multiple mechanisms could account for the proposed health
benefits of ω3 PUFAs. However, with regard to cardioprotection, there is an especially interesting mechanistic
link to altered platelet function and a reduced propensity for thromboembolism. In our Alaskan Native (AN)
population, many of whom still adhere to a traditional marine-based diet, we have found a strong association
between the dietary δ15N biomarker and reduced platelet function. Furthermore, our preliminary data suggest
that CYP4F2*3 gene variation, which defines hepatic vitamin K status, also could be a modifier of platelet
response. Therefore, we have formulated the central hypothesis that both genetic and dietary factors
contribute to inter-individual differences in the basal function of platelets and their response to inhibitors such
as aspirin in AI/AN populations of Alaska and the Northwest. Three specific aims have been designed to test
this hypothesis. In Aim 1 we will determine if the red blood cell δ15N together with genetic variation in CYP4F2
and the aspirin response gene PEAR1, are associated with inter-individual differences in plasma sP-selectin
levels in a cross-section of AI/AN and non-Native populations of Alaska, Washington and Montana. Aim 2 will
test whether there is a difference in platelet ω3 PUFA, thromboxane B2 and 20-HETE concentrations between
individuals with extreme ω3 PUFA intake phenotypes (i.e. the 0-10 and 90-100 percentiles) and whether these
associations are modified by CYP4F2 genotype. Finally, Aim 3 will determine whether, for the same stratified
extremes of ω3 PUFA intake phenotype, there is a difference in platelet aggregation under basal and aspirin-
treated conditions, and whether those associations are modified by CYP4F2 and PEAR1 gene variation.
Collectively, these innovative studies will evaluate unique gene x environment interactions and advance our
understanding of the pharmacogenomics of platelet activation and aspirin drug response in the AN community.

## Key facts

- **NIH application ID:** 9985863
- **Project number:** 5P01GM116691-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kenneth E. Thummel
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $691,629
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985863

## Citation

> US National Institutes of Health, RePORTER application 9985863, PUFAs and gene variation affecting aspirin antiplatelet response (5P01GM116691-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985863. Licensed CC0.

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