DEFB1和PART1遗传变异调控对龋病发生的影响机制研究

龋病是细菌性疾病，与遗传因素有关，迄今机制不明。申请人前期研究发现白裤瑶族人群口腔卫生差但患龋率低。对白裤瑶族龋相关基因多态性研究发现，与汉族和壮族比较，高患龋风险相关的DEFB1 rs11362的T等位基因在白裤瑶族人群中分布较低，低患龋风险相关的PART1 rs27565的T等位基因分布较高。预实验还发现白裤瑶族和汉族牙菌斑微生物存在显著差异。由于DEFB1和PART1均在唾液中表达，且都具有调节免疫和口腔微生物的效应，因此推测DEFB1和PART1可能通过调控牙菌斑微生物结构或功能，影响龋病发生。本项目拟在前期研究基础上采用生物检测技术分析DEFB1和PART1遗传变异对唾液中基因表达的影响，对牙菌斑微生物进行高通量测序，阐明DEFB1和PART1遗传变异及其表达产物与牙菌斑、龋病间的关系，并构建龋病动物模型加以验证，深入探讨白裤瑶族低患龋率的原因，为龋病群体防治提供新思路。

Dental caries is bacteria disease. Dental caries is related to genetic factor, but the mechanism is still unclear. Baikuyao population had low caries with poor oral hygiene were found in our previous studies. The results showed from our genetic research that the proportions of T allele in DEFB1 rs11362 related to high cariogenicity were lower while the proportions of the T allele in PART1 rs27565 related to low cariogenicity were higher in Baikuyao compared to Han and Zhuang population. The study indicated there were significant differences in structure and diversity of the plaque microecology between Baikuyao and Han as well. DEFB1 and PART1 are expressed in saliva. Moreover, both DEFB1 and PART1 have biological effects such as immune regulation and participation in oral flora regulation. Therefore, the study hypothesis is the genetic variation of DEFB1 and PART1 may affect caries development by regulating the microecology of plaque. The aim of this study will explore mechanism of DEFB1 and PART1 on regulation dental plaque microecology and impact on caries through salivary related expression products and promoter activity by using the biological detection technology and animal model of caries, and explain why Baikuyao population had low caries. This study may provide new ideas for the prevention and treatment of dental caries in the whole population.