Protective Effect of the FOXO3 Gene in Cardiometabolic Disease in the CHAMP Cohort

Abstract

Recent findings from the Honolulu Heart Program cohort in Hawaii suggest a longevity-associated variant of FOXO3 may provide resilience against cardiometabolic diseases (CMD), such as hypertension, diabetes, and angina. The present study utilizes data from the Concord Health and Ageing in Men Project (CHAMP) cohort in Australia to further investigate the impact of the longevity associated FOXO3 variant on CMD and longevity. Specifically, the protective ‘G’ allele of rs2802292 was examined for potential protective effects against mortality in individuals with hypertension, diabetes or angina (p-value: 0.01). While no significant impact on mortality was observed in individuals with hypertension or diabetes, a reduced risk of mortality was observed for G allele carriers with angina. These findings are consistent with prior research linking longevity-associated FOXO3 variants to increased lifespan in individuals with heart disease and provide further evidence of its importance as a genetic factor influencing CMD risk. The protective effects against heart disease may arise from FOXO3’s ability to enhance cellular resilience against oxidative stress and regulating metabolic pathways crucial for cardiovascular function. Additional studies are needed to fully understand the mechanisms behind FOXO3’s influence on CMD, in particular heart disease, and to explore its potential for therapeutic development. This research highlights the relevance of genetic factors, specifically FOXO3, in CMD prevention and longevity in the elderly.