BETA-DEFENSINS IN CARIES PRONE CHILDREN

易患龋齿儿童的β-防御素

• 批准号: 6406476
• 负责人: BEVERLY A DALE-CRUNK
• 金额: $ 9.95万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6406476
• 关键词: Hispanic Americans; adolescence (12-20); chemical structure function; clinical research; computer data analysis; cooperative study; defensins; dental caries; dental caries inhibitor; fluorescence spectrometry; gene expression; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human subject; immunogenetics; immunologic assay /test; microorganism growth; microorganism immunology; middle childhood (6-11); nucleic acid sequence; oral bacteria; oral health; rural area; saliva

The beta-defensins are natural antibiotics by oral epithelia and secreted in saliva. These peptides have broad specificity against bacteria, fungi, and some viruses. They are thought to have role in oral health as natural antibiotics. Beta-defensin levels may between individuals, and those with defects in the expression or function of beta-defensins may be susceptible to recurrent infection. Dental caries is an infection; individuals and populations have differing susceptibility to caries. Caries risk is thought to be due to bacterial exposure, diet, and cultural behaviors, but may also be related to biological factors that are due to genetic differences. Beta-defensins may have multiple potential effects on bacteria that colonize the tooth surface, altering biofilm formation, acting directly on bacterial survival, and acting synergistically with other anti-microbial factors. Previous observations on activity, localization and secretion of beta-defensins lead to the hypothesis that the beta-defensins, hBD-1, may be associated with risk for dental caries and that low expression levels, or genetic changes in the function or expression of the peptide, could place an individual at risk for caries. This laboratory has established immunoassays for hBD-1 expression in gingiva and saliva, determined multiple single nucleotide polymorphisms (SNPs) in the DEFB1 gene encoding hBD-1, and examined SNP frequency in different ethnic groups. For this study we have identified a population of Hispanic children in Toppenish, WA, a rural agricultural community near Heritage College, a minority institution that serves Hispanic and Native American students. Appropriately 35% of these children have had 4 or more caries, while nearly 40% gave had no caries. Using these preliminary findings and new SNP assays, the goal of this proposal is to conduct a case- control study to explore the relationship between hBD-1 peptide and caries risk in a group of Hispanic children by determining (1) Do caries- prone children have low levels of hBD-1? and (2) Do caries-prone populations have SNPs in hBD-1 that are associated with caries risk? In addition, we will determine association of individual SNPs with salivary hBD-1 levels. Our project is an exploratory study designed to foster development of genetic tools as risk factors for varies susceptibility. The risk of caries is highly related to under-served populations and minority ethnic groups, therefore, any new approaches may help in directing attention to the problem and care to those in need.

β-防御素是口服上皮的天然抗生素，并在唾液中分泌。这些肽对细菌，真菌和某些病毒具有广泛的特异性。他们被认为在口腔健康中作为天然抗生素起作用。 β-Defensin水平可能在个体之间，以及在β-防御素表达或功能缺陷的患者之间可能容易感染。龋齿是一种感染。个人和人群对龋齿的敏感性不同。龋齿风险被认为是由于细菌的暴露，饮食和文化行为引起的，但也可能与遗传差异引起的生物学因素有关。 β-防御素可能会对细菌具有多种潜在影响，该细菌在牙齿表面定居，改变生物膜的形成，直接作用于细菌存活，并与其他抗微生物因子协同作用。先前关于β-防御素活动，定位和分泌的活动，β-防御素HBD-1的假设可能与龋齿的风险有关，低表达水平或肽功能或表达的遗传变化可能会给龋齿带来风险。该实验室已经建立了在牙龈和唾液中HBD-1表达的免疫测定，确定了编码HBD-1的DEFB1基因中的多个单核苷酸多态性（SNP），并在不同种族中检查了SNP频率。在这项研究中，我们确定了华盛顿州Toppenish的西班牙裔儿童，这是一个遗产学院附近的农村农业社区，这是一个为西班牙裔和美洲原住民学生提供服务的少数民族机构。这些孩子中有35％有4个或更多的龋齿，而将近40％的龋齿没有龋齿。使用这些初步发现和新的SNP分析，该提案的目的是进行案例控制研究，以探索一组西班牙裔儿童中HBD-1肽与龋齿风险之间的关系，通过确定龋齿 - 易于龋齿的孩子的HBD-1水平较低？ （2）容易发生龋齿的人群中有与龋齿风险有关的HBD-1中的SNP？此外，我们将确定单个SNP与唾液HBD-1水平的关联。我们的项目是一项探索性研究，旨在促进遗传工具的开发，因为易感性的风险因素各不相同。龋齿的风险与服务不足的人口和少数族裔群体高度相关，因此，任何新方法都可能有助于将注意力集中在有需要的人身上。