Dental Caries: Whole Genome Association and Gene x Environment Studies

描述(申请人提供)：龋齿(也称为龋齿)仍然是儿童最常见的慢性疾病。尽管总的龋患率在过去40年中有所下降，但乳牙期的龋齿和2-11岁儿童的平均龋患率在过去12年中显著上升。儿童龋病是一个严重的公共卫生问题，因为存在相关的健康问题，而且口腔健康方面的差异导致贫困儿童和服务不足的种族和族裔群体的平均患病率大大提高。这些问题是如此令人担忧，以至于在2005年，美国儿科学会将儿童口腔健康作为他们最关注的领域之一，就像大多数NIDCR“差异中心”一样。多种因素导致个人患龋齿的风险，包括环境因素，如饮食、口腔卫生、氟化物暴露和致龋菌的定植水平，以及宿主因素，如唾液流动。仍然有一些人似乎更容易患龋齿，也有一些人具有极强的抵抗力，无论他们暴露在什么环境风险因素中，这意味着遗传因素在龋病病因中也发挥着重要作用。这一结论得到了人类和动物研究的支持，其中最令人信服的证据来自对分开饲养的双胞胎的研究，在这些研究中，研究人员发现同卵双胞胎(MZ)而不是异卵双胞胎(DZ)在牙齿修复或龋齿表面的百分比上非常相似，并估计基因对龋齿的贡献为40%。尽管有强有力的证据表明基因成分会增加患龋齿的风险，但对龋齿候选基因的研究很少，而且还没有公布全基因组扫描。因此，这项研究的目标是对通过美国多个地点确定的家庭和个人中的大量SNP(500,000或更多)进行龋齿的全基因组关联(GWA)研究。将对三个地点(匹兹堡大学、爱荷华大学和华盛顿大学)的样本进行GWA初步扫描，并在其他合作地点(密歇根大学和加州大学旧金山分校)进行后续研究。这项研究的成功完成将有助于更好地了解龋齿的生物学，并将有助于更早地识别有患龋齿风险的儿童，从而能够改进和有针对性的干预措施。

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.