Gene-Environment Interactions in Glaucoma

青光眼的基因与环境相互作用

基本信息

批准号：
7911024
负责人：
Louis Robert Pasquale
金额：
$ 14.38万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7911024
关键词：
5&apos Untranslated Regions Age Alcohol consumption Alcohols Blindness Blood Blood Vessels Blood flow Candidate Disease Gene Caring Cells Cheek structure Ciliary Body Classification Code Cohort Analysis Cohort Studies Complex DNA DNA Sequence Data Defect Disease Environment Environmental Exposure Environmental Risk Factor Enzymes Estrogens Exons Eye Follow-Up Studies Food Frequencies Funding Genes Genetic Polymorphism Genotype Glaucoma Haplotypes Health Professional Hemostatic function Hormone replacement therapy Hormones Lead Mediating Medical Records Menopause Mutation NOS3 gene Nested Case-Control Study Nitric Oxide Nurses&apos Health Study Optic Disk Optic Nerve Participant Pathway interactions Patient Self-Report Patients Physiologic Intraocular Pressure Population Study Postmenopause Prevention strategy Primary Open Angle Glaucoma Primary Prevention Process Provider Public Health Questionnaires Relaxation Reporting Research Personnel Retinal Ganglion Cells Risk Risk Factors Sampling Single Nucleotide Polymorphism Smooth Muscle Techniques Trabecular meshwork structure Untranslated Regions Up-Regulation Update Variant Vascular Endothelial Cell Visual Fields Woman Women&apos s Health base case control cohort design follow-up gene environment interaction hormone therapy human NOS2A protein human NOS3 protein male men novel optic nerve disorder population based programs prospective

项目摘要

DESCRIPTION (provided by applicant): We propose to investigate whether selected gene-environment interactions are risk factors for primary open angle glaucoma (POAG) in two prospectively followed cohorts of men and women. First, we will determine whether several variants of the endothelial nitric oxide synthase gene (NOS3) are associated with POAG using a nested case-control cohort drawn from our study population. Then, in separate cohort analyses we will study hormone replacement therapy and alcohol consumption in relation to POAG using stratified and multivariate techniques after controlling for important confounders. Finally, we will return to our case-control cohort to ascertain how the interaction between selected NOS3 polymorphisms and our environment exposure alters the risk of developing POAG. The Nurses' Health Study (NHS) began in 1976 among 121,700 women ranging in age from 30 to 55. Approximately 89,000 participants completed a validated semi quantitative food frequency questionnaire (FFQ) in 1980 and every 2-4 years since. The Health Professionals Follow-up Study (HPFS) began in 1986 among 52,000 men ranging in age from 45-75, all of whom completed a FFQ at baseline and every 4 years thereafter. Both groups have been sent a questionnaire biennially to update exposure information and report major illness including POAG. Information has been collected repeatedly on postmenopausal hormone use, alcohol consumption and other related covariates. We have 69,099 DNA samples from NHS participants and 33,545 DNA samples from HPFS participants in storage. In the proposed study we will confirm reports of POAG by contacting the participant's eye care provider, and obtaining pertinent information from the medical record. A self-report of POAG, will be confirmed by systematic record review documenting reproducible visual field loss consistent with glaucomatous optic neuropathy. We anticipate identifying 1246 POAG cases, 909 of which will have DNA samples available for analysis. Overall, the prospective design, large size of the cohorts, the high follow-up rates, repeated assessment of exposures known to alter NOS3 gene activity, and carefully confirmed POAG definition provide a unique opportunity to evaluate several hypotheses of public health importance. The discovery of gene-environment interactions that serve as determinants of POAG could lead to genotype-specific primary prevention strategies for this complex disease.

描述（由申请人提供）：我们建议研究选定的基因环境相互作用是否是前瞻性遵循男女同伴中原发性开角青光眼（POAG）的危险因素。首先，我们将确定使用从我们的研究人群中得出的嵌套病例对照组的内皮一氧化氮合酶基因（NOS3）的几种变体与POAG相关。然后，在单独的队列分析中，我们将在控制重要的混杂因素后使用分层和多元技术研究激素替代疗法和饮酒与POAG有关。最后，我们将返回我们的病例对照组，以确定所选的NOS3多态性与环境暴露之间的相互作用如何改变发展POAG的风险。护士健康研究（NHS）始于1976年的121,700名妇女，年龄在30至55岁之间。大约89,000名参与者在1980年和此后每2-4岁时完成了一份经过验证的半定量食品频率问卷（FFQ）。卫生专业人员的后续研究（HPFS）始于1986年的52,000名男性，年龄在45-75岁之间，他们在基线时完成了FFQ，此后每4年每4年完成了FFQ。两组均两年来都发送了一份问卷，以更新曝光信息，并报告包括POAG在内的重大疾病。已经反复收集有关绝经后激素，饮酒和其他相关协变量的信息。我们有来自NHS参与者的69,099个DNA样品，来自HPFS参与者的33,545个DNA样品。在拟议的研究中，我们将通过联系参与者的眼保健提供者并从病历中获得相关信息来确认POAG的报告。 POAG的自我报告将通过系统的记录审查来证实，记录可再现的视野损失与glaucomatus神经病变一致。我们预计识别1246例POAG病例，其中909例将有可用于分析的DNA样本。总体而言，前瞻性设计，大小的人群，高后续率，重复评估已知会改变NOS3基因活性的暴露以及经过精心确认的POAG定义提供了一个独特的机会，可以评估几种公共健康重要性的假设。作为POAG决定因素的基因环境相互作用的发现可能会导致这种复杂疾病的基因型特异性预防策略。