Genetic and Environmental Factors in Dental Fluorosis

氟斑牙的遗传和环境因素

• 批准号: 7383922
• 负责人: DEBORAH VALULICK DAWSON
• 金额: $ 14.59万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383922
• 关键词: Acquired Dental Fluorosis; Affect; Age; Amoxicillin; Animals; Bone Development; Calcium; Canada; Candidate Disease Gene; Caries prevention; Categories; Child; Cohort Studies; Communities; Complex; Data; Data Analyses; Dental caries; Development; Dietary intake; Environmental Exposure; Environmental Risk Factor; Family; Fluorides; Future; Genes; Genetic; Genetic Materials; Genotype; Goals; Haplotypes; Human; Individual; Intake; Investigation; Iowa; Knowledge; Lead; Light; Mixed Dentition; Molecular; Morphogenesis; Numbers; Nutrient; Odontogenesis; Parents; Pathway interactions; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Play; Population; Predisposition; Prevalence; Prevention; Preventive; Primary Dentition; Range; Recommendation; Recruitment Activity; Relative (related person); Resistance; Risk; Role; Severities; Single Nucleotide Polymorphism; Surface; Time; Tooth structure; Treatment Protocols; Triad Acrylic Resin; Twin Studies; United States; Variant; Vitamin D; Work; base; cohort; fluorosis; gene environment interaction; human study; innovation; mineralization; novel; permanent tooth

DESCRIPTION (provided by applicant): The prevalence of dental fluorosis has increased significantly in recent decades, due primarily to the caries-preventive use of fluoride. The accepted tenet has been that dental fluorosis is a problem that results solely from excessive fluoride intake during the time of tooth development. However, it is becoming increasingly apparent that there is also considerable individual variation in predisposition to fluorosis. In our work with the Iowa Fluoride Study (R01-DE09551), we have observed great variation in fluorosis severity within a given category of fluoride intake. The central hypothesis of this application is that dental fluorosis involves a complex interplay between individual genes (which set the threshold for development of fluorosis) and specific environmental exposures, including dietary patterns of fluoride intake and other nutrients. As part of the Iowa Fluoride Study, a large cohort has already been recruited and maintained for more than 13 years, with detailed longitudinal fluoride intake, dietary intake, and medication usage data, as well as surface-specific fluorosis phenotype data in the primary and mixed dentitions. As part of the Iowa Bone Development Study (R01-DE12101), which utilizes the Iowa Fluoride Study cohort, genetic material has been collected from over 600 cohort children and 970 parents, and genotypes are available for a substantial number of candidate genes potentially related to bone development. The subset of these genes is also reasonable candidates for roles in tooth morphogenesis and mineralization. The proposed secondary data analyses will examine these genes in light of dental fluorosis phenotypes, in order to identify specific genes/pathways that influence fluorosis, and to understand how these genes interact with fluoride and other factors (e.g., calcium intake, medications) to modify an individual's risk for dental fluorosis in both the primary and permanent dentitions. Genetic strategies include population- and family-based (child-parent trio) association studies with single nucleotide polymorphisms (SNPs), as well as specific haplotype analyses. The proposed work will be the first human study to specifically assess genetic factors and gene-environment interaction in dental fluorosis development. The novel information obtained will also assist in planning future studies. Knowledge gained may lead to useful strategies to identify those at increased risk for fluorosis so that more individualized fluoride regimens can be developed and applied.

描述（由申请人提供）：近几十年来，氟斑牙的患病率显著增加，主要是由于预防龋齿使用氟化物。公认的原则是，氟斑牙是一个问题，结果完全是由于过量的氟化物摄入在牙齿发育的时间。然而，越来越明显的是，氟中毒的易感性也有相当大的个体差异。在我们的爱荷华州氟化物研究（R 01-DE 09551）中，我们观察到在给定的氟化物摄入量范围内，氟中毒严重程度存在很大差异。这一应用的核心假设是，氟斑牙涉及个体基因（为氟中毒的发展设定阈值）和特定环境暴露（包括氟化物摄入和其他营养素的饮食模式）之间的复杂相互作用。作为爱荷华州氟化物研究的一部分，已经招募了一个大型队列，并维持了13年以上，提供了详细的纵向氟化物摄入量、饮食摄入量和药物使用数据，以及乳牙和混合牙列中表面特异性氟中毒表型数据。作为利用爱荷华州氟化物研究队列的爱荷华州骨发育研究（R 01-DE 12101）的一部分，从600多名队列儿童和970名父母中收集了遗传物质，并获得了大量可能与骨发育相关的候选基因的基因型。这些基因的子集也是合理的候选人在牙齿形态发生和矿化的作用。拟议的二次数据分析将根据氟斑牙表型检查这些基因，以确定影响氟中毒的特定基因/途径，并了解这些基因如何与氟和其他因素（例如，钙摄入量，药物），以改变一个人的风险，氟斑牙在乳牙和恒牙列。遗传策略包括基于群体和家庭（儿童-父母三人组）的单核苷酸多态性（SNP）关联研究，以及特定的单倍型分析。这项研究将是第一项专门评估氟斑牙发展中遗传因素和基因-环境相互作用的人类研究。获得的新信息也将有助于规划未来的研究。所获得的知识可能会导致有用的策略，以确定那些氟中毒的风险增加，使更多的个性化氟治疗方案可以开发和应用。