Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy  

作　　者：Thomas A Vander Jagt Monica H Neugebauer Marilee Morgan Donald W Bowden Vallabh O Shah 

机构地区：[1]Department of Biochemistry and Molecular Biology,University of New Mexico School of Medicine [2]MIND Institute [3]Center for Diabetes Research,Wake Forest School of Medicine

出　　处：《World Journal of Diabetes》2015年第9期1113-1121,共9页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by The grants from the National Center for Research Resources,No.5P20RR016480-12;The National Institute of General Medical Sciences of the NIH,No.8P20GM103451-12;the partial support from the National Center for Advancing Translational Sciences of the National Institutes of Health,No.8UL1TR000041;the University of New Mexico Clinical and Translational Science Center;the cost for clinical phenotyping and payments to participants was supported under a UNM Health Sciences Center-based Cardiovascular and Metabolic Diseases Signature Program

摘　　要：AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.AIM To examine DNA methylation profiles in a longitudinalcomparison of pre-diabetes mellitus （Pre-DM）subjects who transitioned to type 2 diabetes mellitus（T2DM）.METHODS： We performed DNA methylation studyin bisulphite converted DNA from Pre-DM （n = 11） atbaseline and at their transition to T2DM using IlluminaInfinium HumanMethylation27 BeadChip, that enablesthe query of 27578 individual cytosines at CpG locithroughout the genome, which are focused on thepromoter regions of 14495 genes.RESULTS： There were 694 CpG sites hypomethylatedand 174 CpG sites hypermethylated in progression from Pre-DM to T2DM, representing putative genes involvedin glucose and fructose metabolism, inflammation,oxidative and mitochondrial stress, and fatty acidmetabolism. These results suggest that this highthroughput platform is able to identify hundreds ofprospective CpG sites associated with diverse genesthat may reflect differences in Pre-DM compared withT2DM. In addition, there were CpG hypomethylationchanges associated with a number of genes that maybe associated with development of complications ofdiabetes, such as nephropathy. These hypomethylationchanges were observed in all of the subjects.CONCLUSION： These data suggest that some epigenomicchanges that may be involved in the progression ofdiabetes and/or the development of complications maybe apparent at the Pre-DM state or during the transitionto diabetes. Hypomethylation of a number of genesrelated to kidney function may be an early marker fordeveloping diabetic nephropathy.

关 键 词：EPIGENETIC CHANGES PRE-DIABETES DIABETES NEPHROPATHY 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]