广西红水河流域人群长寿相关基因的筛选和验证

The five counties centering on Bama located at Red river basin of Guangxi are famous longevity zone. The researches of our team and other scholars have confirmed that the longevity in the zone has special environmental and genetic background. But the previous researches aimed at the single known genes inefficiently, and could not find the new longevity genes. Having constructed DNA specimen database，our team will perform the genotypical analysis for 500 cases of the longevity group(the elderly more than 90 years old) and 500 cases of internal control group (the elderly died before 75 years old) from the longevity zone using Human Exome BeadChip in this study and build up the genotype database. Compared the database with the one of 500 cases of external control group(the elderly from districts of Guangxi except red river basin died before 75 years old) by bioinformatics analysis, the candidate genes and loci related to human longevity will be screened. Analysing the distribution difference of these genes and loci between 500 cases from the longevity families and other 500 cases of external control group, they would be validated and identified. Their fuctions will be probed preliminarily. The study aims to identify the new and special longevity genes in the zone and validate the other genes related to human longevity which were found in previous researches. Combined with the epidemiological data, the association analyses including the gene-gene interactions and the gene-environment interactions will be performed, which would lay solid foundation for further research of these longevity genes' functions.

以巴马为中心的广西红水河流域五个县是著名的长寿区。本课题组及其他学者已证实该地区人群长寿有独特的环境和遗传背景。但既往针对基因的研究多是单个已知基因，效率低下，不能发现新的特异性长寿基因。本项目拟利用已建立的DNA标本库，采用外显子组基因芯片对长寿组500人(红水河流域≥90岁长寿老人)和内对照组500人(该地区已在75岁前去世的老人)进行基因分型，生成基因型数据库，与外对照组500人(红水河流域外已在75岁前去世的老人)基因型比对，通过生物信息学方法筛选与长寿相关的候选基因和位点；分析这些基因和位点在另外500名长寿家系成员和另外500名外对照组成员中的分布差异，对其进行确认；对它们的功能进行初步探讨。研究以期发现该地区特异性长寿基因，并对长寿相关的单个基因进行验证。结合环境流行病学调查资料，分析基因-基因和基因-环境间的交互作用及与长寿的关联性，为今后相关基因功能的深入研究打下基础。

本项目拟利用已建立的DNA标本库，采用外显子组基因芯片对长寿人群和对照人群进行基因分型，生成基因型数据库，通过生物信息学方法筛选与长寿相关的候选基因和位点；并对它们的功能进行初步探讨。研究结果发现：1. NHEJ1、ATG7、CPNE4、IMMP2L、ADCY、KCNQ1、AKAP6等20个基因可能和长寿相关.2．KCNQ1基因位点rs151290、rs2237892和rs2237897的多态性可能与广西河池市农村老年人血糖水平上升的风险相关。3. 携带VEGFA基因位点rs2010963、rs25648、rs833070构建的G T T单体型个体的血脂异常风险可能高于非携带G T T单体型个体。4. 广西东兰县老年人群中CDH13基因rs58409508位点携带A等位基因可能使空腹血糖升高风险增加，rs8051657位点携带TT基因型可能使空腹血糖升高风险增加。