This study tested whether 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 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 (HR 1.61; 95% CI 1.44–1.80), P<0.0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82–1.02; p=0.11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = –0.23, p=0.038). 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=0.021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43–1.01; p=0.054 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=0.61) or Okinawan (HR 0.95; 95% CI 0.66–1.38; p=0.79) heritage. The present prospective study found longevity associated FOXO3 genotype did not independently affect risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3 TT genotype may merit particular attention in CAD prevention programs.

中文翻译：

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FOXO3 长寿基因型减轻高血压对中年男性冠状动脉疾病的风险：Kuakini Honolulu 心脏计划


本研究测试了携带 FOXO3 SNP rs2802292 （TG/GG） 的长寿相关 G 等位基因是否能预防高血压男性的冠状动脉疾病 （CAD）。受试者是居住在欧胡岛的美国男性，具有日本 （n=5415） 或冲绳 （n=897） 血统，并且在基线 （1965-1968） 时年龄在 45-68 岁时没有 CAD。在随访期间，有 1,629 例 CAD 事件病例。调整年龄和心血管疾病危险因素后，主效应 Cox 模型显示，在日本血统的男性中，高血压是 CAD 的强预测因子（HR 1.61;95% CI 1.44-1.80），P<0.0001），但 TG/GG 基因型与 CAD 无关（HR 0.92;95% CI = 0.82-1.02;p=0.11）。完整的 Cox 模型显示 TG/GG 与高血压的相互作用是显著的 （β = –0.23，p = 0.038）。按高血压状态分层，TG/GG 基因型 TG/GG 在每组中对 CAD 具有保护作用（日本血统男性 HR 0.83;95% CI 0.71-0.96;p=0.021，冲绳血统男性 HR 0.66;95% CI 0.43-1.01;p=0.054）。在具有日本血统 （HR 1.04;95% CI 0.89–1.22;p=0.61） 或冲绳血统 （HR 0.95;95% CI 0.66–1.38;p=0.79） 血统的正常血压男性中，未见与 CAD 相关。目前的前瞻性研究发现，与长寿相关的 FOXO3 基因型并不独立影响所有男性患 CAD 的风险。相反，它与高血压男性对 CAD 事件的保护有关。在 CAD 预防计划中，具有 FOXO3 TT 基因型的高血压中年男性可能值得特别关注。