DNA甲基化与广西巴马地区长寿的相关性

The correlationship of DNA methylation and longevity in Guangxi Bama region

目的探讨DNA甲基化与巴马长寿的关系。方法在广西巴马县长寿家族中选取60例90~110岁老人组成长寿组,在非长寿家族中选取48~85岁的健康者60例组成对照组。抽取外周血2 ml,构建DNA混合池,利用Roche-Nimble Gen甲基化芯片技术对研究人群的全基因组进行扫描,使用SPSS17.0软件及在线分子功能注释系统(MAS)进行数据分析,P<0.01视为甲基化程度较高的序列。结果共筛查出6 441个超甲基化位点,其中长寿组392个,对照组6 049个。高甲基化位点共涉及1 618个基因,长寿组有133个,对照组有1 485个。两组人群的高甲基化基因均涉及24个生物学功能,均以细胞过程、生理过程、生物调控为主。长寿组高甲基化基因涉及42个信号通路,对照组涉及156个信号通路。长寿组和对照组中均有与年龄相关性疾病有关联的高甲基化基因,长寿组中涉及较多疾病的基因有CCKBR、COL18A1、EGR3、H19、IL11、TIMP1、S100A1等;对照组中涉及较多疾病的基因有ACSL1、ADAMTS13、ADCY8、AHRR、ARVCF、ATP2A1、ATP5I、BCS1L、GCK、ITGA2B等。结论本研究利用芯片技术筛查获得了与长寿呈正相关和负相关的高甲基化位点、基因及其生物学功能分类、信号通路,为DNA甲基化和长寿的深入研究提供了基础数据。

Objective To seek for hypermethylation sites and genes,and explore the correlationship between DNA methylation and longevity in Guangxi Bama. Methods Sixty aged people with long-live family history from 90 to 11 o years old were recruited into longevity group,and another sixty individuals without long-live family history aged from 48 to 85 were recruited into control group. 2 ml peripheral blood was extracted to construct the DNA gene pools,then the whole genome was scanned by the Roche Nimble Gen methylation array technology,and the final data was analyzed by SPSS17. 0 software and the online molecular functional annotation system,it was significant difference when P<0. 01. Results 6 441 hypermethyaltion sites were screened out,392 sites for the longevity group and 6 049 sites for the control group. The hypermethylation sites involved in 1 618 genes,133 hypermethylation genes for the longevity group and 1 485 ones for the control group. The hypermethylation genes from both groups involved in 24 biological function annotations,mainly locating on the cellular process,physiological process and biological regulation. The hypermethylation genes from longevity group involved in 42 signal pathways and 156 signal pathways for the control group. The hypermethylation genes in both groups were related to the age-dependent diseases,and there were CCKBR,COL18A1,EGR3,H19,IL11,TIMP1,S100A1 and so on in longevity group which were highly correlated with different diseases,while there were ACSL1,ADAMTS13,ADCY8,AHRR,ARVCF,ATP2A1,ATP5 I,BCS1L,GCK,ITGA2 B and so on in control group which were highly correlated with much diseases. Conclusions Hypermethylation sites and gens negatively or positively correlating to longevity are screened out which are involved in many functional annotations and signal pathways,which provide basic clues for further research on the DNA methylation and longevity.