Insulin-resistance and depression cohort data mining to identify nutraceutical related DNA methylation biomarker for type 2 diabetes  

作　　者：Fengji Liang Yuan Quan Andong Wu Ying Chen Ruifeng Xu Yuexing Zhu Jianghui Xiong 

机构地区：[1]Lab of Epigenetics and Advanced Health Technology,SPACEnter Space Science and Technology Institute,Shenzhen,Guangdong Province,518117,PR China [2]State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center,Beijing,100094,PR China [3]School of Computer Science and Technology,Harbin Institute of Technology Shenzhen Graduate School,Shenzhen,Guangdong Province,518055,PR China

出　　处：《Genes & Diseases》2021年第5期669-676,共8页基因与疾病（英文）

基　　金：This research was funded by the grants from the Science,Technology and Innovation Commission of Shenzhen Municipality[grant numbers JCYJ20151029154245758,CKFW2016082915204709].

摘　　要：Insulin-resistance(IR)is one of the most important precursors of type 2 diabetes(T2D).Recent evidence suggests an association of depression with the onset of T2D.Accumu-lating evidence shows that depression and T2D share common biological origins,and DNA methylation examination might reveal the link between lifestyle,disease risk,and potential therapeutic targets for T2D.Here we hypothesize that integrative mining of IR and depression cohort data will facilitate predictive biomarkers identification for T2D.We utilized a newly proposed method to extract gene-level information from probe level data on genome-wide DNA methylation array.We identified a set of genes associated with IR and depression in clin-ical cohorts.By overlapping the IR-related nutraceutical-gene network with depression net-works,we identified a common subnetwork centered with Vitamin D Receptor(VDR)gene.Preliminary clinical validation of gene methylation set in a small cohort of T2D patients and controls was established using the Sequenome matrix-assisted laser desorption ionization-time flight mass spectrometry.A set of sites in the promoter regions of VDR showed a signifi-cant difference between T2D patients and controls.Using a logistic regression model,the optimal prediction performance of these sites was AUC Z 0.902,and an odds ratio Z 19.76.Thus,monitoring the methylation status of specific VDR promoter region might help stratify the high-risk individuals who could potentially benefit from vitamin D dietary sup-plementation.Our results highlight the link between IR and depression,and the DNA methyl-ation analysis might facilitate the search for their shared mechanisms in the etiology of T2D.

关 键 词：DEPRESSION DNA methylation Insulin resistance NUTRACEUTICALS Type 2 Diabetes Vitamin D receptor 

分 类 号：R587.1[医药卫生—内分泌]