Chen Randi, Morris Brian J, Donlon Timothy A, Nakagawa Kazuma, Allsopp Richard C, Willcox Bradley J, Masaki Kamal H
Department of Research, Kuakini Honolulu Heart Program, Center of Biomedical Research Excellence (COBRE) for Clinical and Translational Research on Aging, Kuakini Medical Center, Honolulu, Hawaii.
School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia.
J Gerontol A Biol Sci Med Sci. 2024 Dec 1;79(12). doi: 10.1093/gerona/glae254.
This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.
Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years.
During the follow-up, there were 1 629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.44-1.80), p < .0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p = .11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p = .038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p = .021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p = .054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p = .61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p = .79) heritage.
The present prospective study found that longevity-associated FOXO3 genotype did not independently affect the risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3TT genotype may merit particular attention in CAD prevention programs.
本研究旨在测试携带长寿相关的FOXO3单核苷酸多态性rs2802292的G等位基因（TG/GG）是否能预防高血压男性患冠心病（CAD）。
研究对象为居住在瓦胡岛的美国男性，他们有日本血统（n = 5415）或冲绳血统（n = 897），在基线时（1965 - 1968年）年龄为45 - 68岁，且无CAD。
在随访期间，有1629例CAD病例。在调整年龄和心血管疾病风险因素后，主效应Cox模型显示，在日本血统男性中，高血压是CAD的强预测因素（风险比[HR] 1.61；95%置信区间[CI] 1.44 - 1.80），p <.0001），但TG/GG基因型与CAD无关（HR 0.92；95% CI = 0.82 - 1.02；p =.11）。完整的Cox模型显示TG/GG与高血压的相互作用显著（β = -0.23，p =.038）。按高血压状态分层，TG/GG基因型在每组中对CAD均有保护作用（在日本血统男性中，HR 0.83；95% CI 0.71 - 0.96；p =.021；在冲绳血统男性中，HR 0.66；95% CI 0.43 - 1.01；p =.054）。在血压正常的日本血统（HR 1.04；95% CI 0.89 - 1.22；p =.61）或冲绳血统（HR 0.95；95% CI 0.66 - 1.38；p =.79）男性中未发现与CAD有关联。
本前瞻性研究发现，与长寿相关的FOXO3基因型并非在所有男性中都独立影响CAD风险。相反，它与预防高血压男性患CAD有关。携带FOXO3TT基因型的高血压中年男性在CAD预防项目中可能值得特别关注。
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