基于家系的广西巴马人群氧化应激基因多态性及其与长寿相关表型的关联性研究

广西巴马县是全国著名的长寿地区，为研究遗传因素与长寿的关系提供了条件。项目根据前期研究结果及文献复习，选择HSP70、FOXO3A、SIRT6、PON1等四个氧化应激相关基因并挑选代表性SNPs，设置巴马县长寿家系组、非长寿家系组（内对照组）和巴马县以外地区非长寿家系组（外对照组），每组每个家系取老中青三代各一名成员为研究对象，对研究对象进行问卷调查、体格检查、采集血样标本，检测HSP70等四个基因的多态性、启动子的甲基化水平和mRNA表达水平，检测MnSoD和GADD45两个下游调控靶基因的mRNA表达水平，检测血清中的SOD、MDA含量。分析四个基因多态性与巴马长寿的关系、与其相应启动子甲基化水平的关系、与MnSoD和GADD45基因转录水平的关系及与相关表型的关联，并探讨四个基因之间可能存在的基因-基因和基因-环境交互作用。研究结果将为今后进一步的巴马长寿机制探讨提供新的线索和方向。

Bama County of Guangxi is the famous longevity area and it provides conditions for research on relationship between genetic factors and longevity. Based on our previous studies and literature review, we choose four oxidative stress-related genes(HSP70、FOXO3A、SIRT6、PON1)and select tags SNPs , and set three groups including the group of longevity families in Bama, the group of non-longevity families in Bama ( internal control group), and the group of non-longevity families outside Bama ( the external control group). One person will be selected from one generation of the old, middle-aged and young generations in one family as research objects. They will be taken questionnaire investigation, physical examination and blood specimen collection. The following detections will be conducted in all objects. These are the four genes'polymorphisms, DNA methylation level, mRNA expression, MnSoD and GADD45 genes'mRNA expression and the contents of SOD、MDA in sera. The relations among oxidative stress-related genes polymorphisms, the DNA methylation level, Bama Longevity, the mRNA expression of MnSoD and GADD45 genes and longevity-related Phenotypes will be analyzed. Besides, the gene-gene interaction among four genes and gene-environment interaction will also be explored. The results of this program will provide new clues and thinkings for the further research on the genetic mechanism of Bama Longevity.