# APOE ε4 and ischemic heart disease in American Indian/Indigenous tribal Elders

**Authors:** Rene Labounek, Matti J. Matheson, Ashley J. Petersen, Adam Hansen, Adam D. Block, Corey Strong, Annamarie Hill, Meghan Kremer, Ann J. Robertson, Valmiki Maharaj, Kamakshi Lakshminaryan, Danni Li, J. Neil Henderson, Igor Nestrasil, Christophe Lenglet, William G. Mantyh

PMC · DOI: 10.1016/j.ahjo.2025.100662 · American Heart Journal Plus: Cardiology Research and Practice · 2025-11-04

## TL;DR

This study explores how the APOE ε4 gene variant is linked to heart disease in American Indian tribal Elders.

## Contribution

The study quantifies the association between APOE ε4 and ischemic heart disease in American Indian populations.

## Key findings

- APOE ε4 allele increases the odds of ischemic heart disease 2.38-fold in AI tribal Elders.
- APOE ε4 prevalence is high in the studied American Indian community.

## Abstract

American Indian/Indigenous (AI) populations have the highest rate of ischemic heart disease (IHD) of any racial or ethnic group in the United States. While modifiable cardiovascular risk factors represent a well-established source of elevated IHD in AI, little is known regarding genetic IHD influences, in particular APOE ε4, which has an ancestry-dependent prevalence and effect on human disease. We sought to quantify the prevalence and association between APOE ε4 and IHD in AI communities.

We performed a cross-sectional, community-based study including tribal Elders (ages >54 years) at the Bois Forte Band of Chippewa in the state of Minnesota. We collected data pertaining to demographics, cardiovascular risk factors, APOE ε4 genotype, and ischemic heart disease (defined as history of myocardial infarction, coronary artery bypass graft, angiogram showing coronary artery disease, percutaneous transluminal coronary angioplasty, or thrombolytic therapy).

One-hundred-eighty-one participants were included. Their median age and interquartile range were 67 (61, 73) years, AI ancestry was 75 % (50 %, 100 %), 126 (70 %) were females, 46 (25 %) were APOE ε4 heterozygous, and 5 (2.8 %) were APOE ε4 homozygous. Each APOE ε4 allele increased the odds of IHD in AI tribal Elders 2.38-fold (95 % CI: 0.94–6.89; p = 0.06), which is comparable to a two-point rise in hemoglobin A1C.

APOE ε4 appears to play an important role in the risk of IHD in AI populations, given its high prevalence and strong association with IHD.

## Linked entities

- **Diseases:** ischemic heart disease (MONDO:0024644)

## Full-text entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}
- **Diseases:** coronary artery disease (MESH:D003324), IHD (MESH:D017202), myocardial infarction (MESH:D009203)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A1C

## Full text

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12639555/full.md

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Source: https://tomesphere.com/paper/PMC12639555