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The FoxO3 gene and cause-specific mortality.

Bradley J Willcox1,2, Gregory J Tranah3, Randi Chen1

  • 1Department of Research, Kuakini Medical Center, Honolulu, HI, 96817, USA.

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|April 14, 2016
PubMed
Summary

The G allele of the FOXO3 gene is linked to longer life. Carriers of this longevity-associated gene showed a 10% reduced risk of death, primarily due to lower rates of coronary heart disease (CHD).

Keywords:
FOXO3heart diseaselongevitymortality

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Area of Science:

  • Genetics
  • Gerontology
  • Epidemiology

Background:

  • The FOXO3 gene, specifically the G allele of SNP rs2802292, has been consistently associated with longevity across diverse global populations.
  • Understanding the specific mortality risks and causes of death linked to this longevity-associated genotype is crucial for aging research.

Purpose of the Study:

  • To quantify the mortality risk associated with the longevity-associated FOXO3 genotype (rs2802292 G allele).
  • To identify specific causes of death linked to this allele in older American men of diverse ancestry.

Main Methods:

  • A 17-year prospective cohort study of 3584 older Japanese American men (Honolulu Heart Program).
  • A 17-year prospective replication study of 1595 white and 1056 black elderly individuals (Health Aging and Body Composition cohort).
  • Cox proportional hazards models were used to assess cause-specific mortality (coronary heart disease, cancer, stroke) and all-cause mortality in relation to FOXO3 genotype.

Main Results:

  • Carriers of the FOXO3 G allele demonstrated a combined 10% reduction in all-cause mortality risk across Japanese, white, and black populations (HR=0.90).
  • This survival advantage was predominantly driven by a 26% lower risk of death from coronary heart disease (CHD) (HR=0.74).
  • No other significant cause-specific mortality reductions were observed for G allele carriers.

Conclusions:

  • At older ages, carrying the FOXO3 G allele is associated with a significant reduction in overall mortality, primarily due to decreased CHD mortality.
  • These findings highlight FOXO3 and its protein product as potential therapeutic targets for aging-related diseases, especially cardiovascular disease.