Background 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. Methods 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. Results 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. Conclusions 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.

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


背景 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）。方法 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。结果 随访期间，CAD 病例 1 629 例。调整年龄和心血管疾病风险因素后，主效应 Cox 模型显示，在日本血统的男性中，高血压是 CAD 的强预测因子 （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是显著的 （β = –0.23，p = .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 = .021，冲绳血统男性 HR 0.66;95% CI 0.43-1.01;p = .054）。在具有日本血统 （HR 1.04;95% CI 0.89–1.22;p = .61） 或冲绳 （HR 0.95;95% CI 0.66–1.38;p = .79） 血统的正常血压男性中，未见与 CAD 相关。结论 本前瞻性研究发现，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 FOXO3TT 基因型的高血压中年男性可能值得特别关注。