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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Longevity-Associated FOXO3 Genotype and its Impact on Coronary Artery Disease Mortality in Japanese, Whites, and Blacks: A Prospective Study of Three American Populations
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Longevity-Associated FOXO3 Genotype and its Impact on Coronary Artery Disease Mortality in Japanese, Whites, and Blacks: A Prospective Study of Three American Populations

机译：寿命相关的FoxO3基因型及其对日语，白人和黑人冠状动脉疾病死亡的影响：对三种美国人的前瞻性研究

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Background: We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail. Methods: We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study. Results: Multivariate Cox regression models demonstrated that carriage of the longevity-associated G allele of FOXO3 single nucleotide polymorphisms rs2802292 was a protective factor against CAD mortality in all three populations. In Japanese and Whites, but not in Blacks, the protective effect of the G allele was little changed in models adjusted for other major risk factors. Population-attributable risk (PAR) models found that the nonprotective TT genotype contributed 15%, 9%, and 3% to CAD mortality risk in Japanese, White, and Black Americans, respectively, and was one of the top three contributing factors to CAD mortality. In Japanese, this effect size was comparable with hypertension (15%), but in Whites and Blacks PAR for hypertension was higher (29% and 26%, respectively). G-allele carriers had lower plasma TNF-a than noncarriers, suggesting inflammation as a potential mediating factor for CAD mortality risk. Conclusion: FOXO3 genotype is an important risk factor for CAD mortality in older populations. More research is needed to identify potential mechanisms and targets for intervention.
机译：背景：我们最近报道，预防冠状动脉疾病（CAD）死亡率是与FOXO3基因型相关的长寿的主要因素。本研究更详细地研究了这种关系。方法：我们对来自Kuakini-Honolulu心脏项目队列的3584名日本裔美国老年男性和来自健康老龄化和身体成分研究的1595名白人和1067名黑人老年人进行了15年的观察研究。结果：多变量Cox回归模型显示，携带FOXO3单核苷酸多态性rs2802292的长寿相关G等位基因是三个人群中抵抗CAD死亡率的保护因素。在日本人和白人中，但在黑人中，G等位基因的保护作用在调整了其他主要危险因素的模型中几乎没有变化。人群归因风险（PAR）模型发现，非保护性TT基因型在日本、美国白人和黑人中分别占CAD死亡率风险的15%、9%和3%，是导致CAD死亡率的三大因素之一。在日本，这种效应大小与高血压（15%）相当，而白色派和黑人的高血压标准杆数分别为29%和26%。G等位基因携带者的血浆TNF-α水平低于非携带者，表明炎症是冠心病死亡风险的潜在中介因素。结论：FOXO3基因型是老年人群冠心病死亡的重要危险因素。需要进行更多研究，以确定干预的潜在机制和目标。

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