Diet and Lifestyle Factors Reducing Risk for Age-Related Eye Disease

描述(申请人提供)：这项申请是为了继续我们的“饮食和生活方式因素降低年龄相关眼病风险”的研究，并解决国家眼科研究所的研究重点，即“描绘环境和遗传作为视网膜疾病风险因素的相互作用的作用。”这些研究的独特之处在于对维生素D状态、类胡萝卜素状态和广泛健康饮食模式评分的重要性进行了评估。这是全球范围内最大的样本，既包括记录老年性黄斑变性阶段的眼睛照片，也包括对发生这种情况的眼睛黄斑中类胡萝卜素密度的测量。之前的资金允许收集最全面的一组营养数据，以评估年龄相关性黄斑变性(AMD)患病率较低的预测因素，在美国三个州的50-79岁女性中，年龄相关眼病研究中的胡萝卜素平均晚6年(N=1,787)。因为眼睛照片可以识别早期的变化，在大多数女性意识到它们的存在之前，我们能够研究可能影响早期阶段的可改变的饮食和生活方式习惯。我们最近报道了支持维生素D、黄斑类胡萝卜素、叶黄素和玉米黄质的保护作用、健康的饮食模式和体力活动对AMD早/中期发展的保护作用的证据。有强有力的证据表明，这些早期变化对发展到高级阶段具有很强的预见性。然而，这些先前的估计是不同遗传倾向的人患AMD的关联强度的“平均值”。该项目是妇女健康倡议的辅助项目，可以从储存的血液样本中获取DNA，我们将使用这些DNA来确定妇女的高危基因类型，这些基因在最近的大型研究中强烈预测了AMD的风险，并确定了维生素D和视网膜类胡萝卜素状况良好的妇女的特征。我们将使用这些数据来计算遗传风险等级分数，以反映AMD的总体遗传易感性水平。然后，我们将评估在遗传风险得分较高的人群中，与得分较低的女性相比，健康饮食和生活方式与AMD之间的关联是否具有优势。这些关于基于遗传易感性的营养因素重要性范围的见解将有助于确定医生和公共卫生官员可以用来向人们提供可能降低AMD发病和恶化风险的饮食的战略，以最大限度地受益的人为目标，并激励人们采取预防策略。最近与类胡萝卜素和维生素D状态相关的候选基因的基因分型的增加也可能提出新的AMD遗传预测因子，并提供关于叶黄素、玉米黄质和维生素D预防AMD的机制的见解。 公共卫生相关性：我们最近报告的证据支持维生素D、黄斑类胡萝卜素、叶黄素和玉米黄质的保护作用，健康的饮食模式和体力活动对AMD早期/中期的发展具有保护作用。这些研究进一步评估了AMD的遗传易感性是否进一步增强了健康饮食和健康生活方式的保护益处。医生和公共卫生官员可以利用这些发现来告知人们健康的习惯，这些习惯可能会降低发展和恶化AMD的风险，瞄准将受益最大的人，并激励人们采取预防策略。这些变化可能会极大地降低用于治疗老年性黄斑变性的医疗支出，预计在未来几十年，随着美国人口老龄化，老年黄斑变性的医疗支出将增加。

DESCRIPTION (provided by applicant): This application is to continue our studies of "Diet and Lifestyle Factors Reducing Risk for Age-Related Eye Disease" and addresses the National Eye Institute's priority for research to "Delineate the interacting roles of the environment and genetics as risk factors for retinal disease." Unique to these studies is the assessment of the importance of vitamin D status, carotenoid status and scores on broad healthy diet patterns. This is the largest sample, world-wide, that incorporates both eye photographs which document stages of age-related macular degeneration and measurements of the density of the carotenoids in the macula of the eye, where this condition develops. Previous funding has permitted the collection of the most comprehensive set of nutritional data available to evaluate as predictors of lower prevalence of age-related macular degeneration (AMD), an average of six-years later in women 50-79 years of age from three US states in the Carotenoids in Age- Related Eye Disease Study (N=1,787). Because eye photographs identify early changes, before most women are aware of their presence, we were able to study modifiable dietary and lifestyle habits during periods of time when they are likely to influence early stages. We recently reported evidence to support protective roles of vitamin D, the macular carotenoids, lutein and zeaxanthin, healthy diet patterns and physical activity against the development of early/intermediate stages of AMD. There is strong evidence that these early changes are highly predictive of developing advanced stages. However, these previous estimates are "averages" of the strength of associations across people who differ in genetic propensity for developing AMD. This project, which is ancillary to the Women's Health Initiative, has access to DNA from stored blood samples which we will use to characterize women for high risk genotypes which have strongly predicted risk for AMD in recent large studies and to characterize women with good status of vitamin D and retinal carotenoids. We will use these data to calculate genetic risk rank scores reflect level of overall genetic susceptibility to AMD. We will then evaluate whether the strengths of associations of healthy diets and lifestyles to AMD in people who have high, genetic risk rank scores, compared with women who have low scores. These insights about the range of importance of nutritional factors based on genetic susceptibility will help identify strategies that physicians and public health officials can use to inform people of diets that may lower risk for developing and worsening AMD, to target people who will benefit most, and to motivate people to adopt preventive strategies. The addition of genotyping for candidate genes which have recently been related to the status of carotenoids and vitamin D may also suggest new genetic predictors of AMD and provide insights about mechanisms by which lutein and zeaxanthin, and vitamin D, protect against AMD. PUBLIC HEALTH RELEVANCE: We recently reported evidence to support protective roles of vitamin D, the macula carotenoids lutein and zeaxanthin, healthy diet patterns and physical activity against the development of early/intermediate stages of AMD. These studies further evaluate whether being genetically susceptible for developing AMD further enhances the protective benefit of healthy diets and healthy lifestyles. The findings can be used by physicians and public health officials to inform people of healthy habits which may lower risk for developing and worsening AMD, to target people who will benefit most, and to motivate people to adopt preventive strategies. These changes could dramatically lower health care expenditures devoted to treating age-related macular degeneration which are expected to rise as the United States population ages in the coming decades.