白裤瑶族龋相关基因多态性与低患龋率关系研究

Studies have shown that genes may influence the development and progression of dental caries. The population genetics can be used to explore the relationship between Gene and genotype frequencies and the genetic structure, and also association of effects on the selection, mutation, migration and genetic drift of genotype frequencies with genetic structure. .The Baikuyao populations are a branch of the Yao ethnic group in southwest China. They have special habits associated with their traditional lifestyle. Our previous studies demonstrated that the prevalence of caries was significantly lower in the Baikuyao compared with other ethnic minority groups, such as the Han and Zhuang populations and the national average level for China. The underline mechanisms are not well understood. The genetics or lifestyle may contribute to these differences. .Seven hundred Baikuyao and 300 Han subjects will be selected using random and stratified approach. Information about environmental factors including diet, frequency of tooth brushing, fluoride toothpaste usage etc will be collected by questionnaire. Twenty-four candidate gene loci found by GWAS will be genotyped via Sequesnom Mass ARRAY to investigate their association with low caries experience. The genotyping results of Baikuyao will be compared to that of the human genome database Chinese Han and Local Han people. The different group in Baikuyao family were analyzed and compared. The interaction of gene-gene and gene-environment on caries will also be analyzed via crossover analysis, logistic regression and generalized multifactor dimensionality reduction, GMDR in order to explore the association of low caries experience in Baikuyao population of China with caries-related gene polymorphisms.

研究表明遗传基因可能影响龋病发生发展过程，利用群体遗传学研究方法，研究基因和基因型频率及影响这些频率的选择效应、突变、迁移及遗传漂变作用与遗传结构的关系，可探讨龋病发生发展的机制。本团队前期研究结果表明，有严格族内婚姻制及独特生活习俗、相对封闭的广西白裤瑶人群患龋率低于同地区具有相似生活习惯及氟化物暴露的汉族居民，也低于广西及全国平均患龋水平，据此推测其群体遗传学因素可能十分关键。本项目随机抽取700例白裤瑶族居民为研究对象和300例同地区汉族居民为对照，采用Mass ARRAY分子量阵列技术在全基因组关联研究（GWAS）新发现的24个龋相关候选基因基础上，进行单核苷酸多态性（SNP）的基因分型，将分型结果与人类基因组数据库中中国汉族人群、同地区汉族居民、白裤瑶族内组内及家系等进行分析比较，找出基因频率和基因型频率差异，结合问卷及现场环境因素调查结果，探索龋相关基因多态性与低患龋率关系。

项目的背景：研究表明遗传基因可能影响龋病发生发展过程，利用群体遗传学研究方法，研究基因和基因型频率及影响这些频率的选择效应、突变、迁移及遗传漂变作用与遗传结构的关系，可探讨龋病发生发展的机制。.主要研究内容：.在河池市南丹县随机抽取白裤瑶族、汉族及壮族的12岁儿童共1184人进行口腔检查和问卷调查，并采用SNPscan高通量单核苷酸多态性（SNP）分型技术对48个龋相关候选基因进行分型，并分析SNP与龋病关系及在民族间的分布差异。进一步进行环境-基因交互作用及家系遗传分析，探索白裤瑶族低患龋率的原因。.重要结果及关键数据.项目实际完成调查1076名学生，包括277名汉族、344名壮族、446名白裤瑶族儿童。口腔检查结果显示，白裤瑶族儿童患龋率38.8%，低于汉族51.3%和壮族儿童48.3%。环境因素分析发现甜食摄入频率与龋病呈正相关，有牙石牙数与龋病呈负相关关系，白裤瑶族甜食摄入频率较低。基因分析显示，与低患龋风险相关的PART1 rs27565 T等位基因在白裤瑶族分布较高、而与高患龋风险相关的DEFT1 rs11362 T等位基因在白裤瑶族分布较低。基因-基因/环境交互作用研究发现，rs11362、rs27565与民族、牙石牙数、刷牙频率存在交互作用。家系关联性分析提示，GLUT2、MPPED2、AJAP1、LYZL2、ACTN2基因可能与白裤瑶族龋病遗传易感性相关。白裤瑶族较低的糖摄入频率及龋相关基因多态性的民族异质性和分布差异是白裤瑶族儿童患龋率较低的主要原因。.科学意义：为了解宿主对龋病的防御机制提供线索，还可以为易感高危人群的提供特殊口腔卫生指导以及为未来龋病的基因诊断、基因治疗和防龋基因药物的研究提供依据。