Dental Caries: Whole Genome Association and Gene x Environment Studies

龋齿：全基因组关联和基因 x 环境研究

• 批准号: 8035614
• 负责人: Mary L. Marazita
• 金额: $ 10万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035614
• 关键词: Academy; Age; American; Animals; Area; Asthma; Behavioral; Biology; Buffers; California; Candidate Disease Gene; Characteristics; Child; Childhood; Chronic Disease; Dental Enamel; Dental Hygiene; Dental caries; Diet; Disease; Dizygotic Twins; Early identification; Environment; Environmental Risk Factor; Ethnic group; Etiology; Exhibits; Family; Fluorides; Follow-Up Studies; Funding; Gender; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Health; Health Care Costs; Heritability; Human; Individual; Integration Host Factors; Intervention; Iowa; Lead; Michigan; National Institute of Dental and Craniofacial Research; Oral health; Pediatrics; Persons; Phase; Phenotype; Play; Positioning Attribute; Poverty; Prevalence; Primary Dentition; Public Health; Publishing; Relative (related person); Research Personnel; Resistance; Risk; Role; SNP genotyping; Salivary; Sampling; San Francisco; Site; Surface; Time; Tooth structure; Twin Studies; Universities; Washington; base; cariogenic bacteria; case control; early childhood; environmental allergy; genome wide association study; genome-wide; improved; kindergarten; programs; racial and ethnic; tooth surface

DESCRIPTION (provided by applicant): Dental caries (also known as tooth decay) remains the most common chronic disease of childhood. Although overall caries prevalence has declined over the last 40 years, dental caries in the primary dentition and mean caries rates in children ages 2-11 has increased markedly over the past 12 years. Childhood caries is a serious public health issue because of associated health problems and because disparities in oral health have led to substantially higher average disease prevalence among children in poverty and in underserved racial and ethnic groups. These issues are of such concern that in 2005, the American Academy of Pediatrics made children's oral health one of their top areas of focus, as it is for the majority of the NIDCR "Disparities Centers." Multiple factors contribute to a person's risk for caries, including environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and host factors such as salivary flow. There are still individuals who appear to be more susceptible to caries and those that are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Despite the strong evidence of a genetic component to risk for dental caries, there have been only a few studies of candidate genes in caries, and no published genome-wide scans. Therefore, the goal of this study is to perform genome-wide association (GWA) studies of dental caries with a large panel of SNPs (500,000 or more) in families and individuals ascertained through multiple US sites. There will be an initial GWA scan in samples from three sites (University of Pittsburgh, University of Iowa, and University of Washington), with follow-up studies in additional collaborating sites (University of Michigan and UCSF). Successful completion of this study will allow a better understanding of the biology of dental caries, and will lead to earlier identification of children at risk for dental caries, thereby allowing improved and targeted interventions.

描述（由申请人提供）：龋齿（也称为牙齿腐烂）仍然是最常见的儿童慢性疾病。尽管过去40年中的总体龋齿患病率下降了，但在过去的12年中，主要牙列龋齿和2-11岁儿童的平均龋齿率显着增加。儿童龋齿是一个严重的公共卫生问题，因为相关的健康问题，并且由于口腔健康的差异导致贫困儿童和服务不足的种族和种族群体的平均疾病患病率显着较高。这些问题令人关注，以至于2005年，美国儿科学会使儿童口腔健康成为其主要重点领域之一，就像大多数NIDCR“差异中心”一样。多种因素有助于一个人的龋齿风险，包括饮食，口腔卫生，氟化物暴露以及肉毒原菌的定殖水平以及宿主因素（例如唾液流量）。仍然有些人似乎更容易受到龋齿的影响，而不管他们暴露的环境危险因素如何，也有极大的抗性，这意味着遗传因素在龋齿病因学中也起着重要作用。这一结论得到了人类和动物的研究的支持，其中最令人信服的证据来自对单双胞胎的研究，研究人员发现了单卵双胞胎（MZ）内的相似之处，但在牙齿（DZ）双对中却不相似，而牙齿的百分比恢复了牙齿，并且对Carie的遗传贡献为40％。尽管有强有力的证据表明龋齿风险有遗传成分，但在龋齿中只有少数候选基因的研究，也没有发表的全基因组扫描。因此，这项研究的目的是对龋齿进行全基因组关联（GWA）研究，并在通过多个美国地点确定的家庭和个体中使用大量的SNP（500,000或更多）进行牙科研究。将在三个地点（匹兹堡大学，爱荷华大学和华盛顿大学）的样品中进行最初的GWA扫描，并在其他合作地点（密歇根大学和UCSF）进行了后续研究。这项研究的成功完成将使您可以更好地了解龋齿的生物学，并将导致早期识别有龋齿风险的儿童，从而可以改善和有针对性的干预措施。