title: Genome-wide DNA methylation analysis in Graves' disease.
abstract: As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathogenesis of GD. Here, we for the first time reported the DNA methylation pattern in GD through a high-throughput analysis. In order to investigate genome-wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and Nimblegen human DNA methylation 3 × 720 K promoter plus CpG island microarrays were used to identify differentially methylated regions (DMRs) from blood samples in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation state of candidate genes. Transcription level of each gene was estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in GD patients and normal controls was significantly different (p<0.05). In the female group, significantly decreased methylation was observed in GD patients compared with normal controls (p<0.05). The transcription of ICAM1 at the mRNA level was significantly higher in GD patients compared with normal controls (p<0.05). Besides, the transcription of DNMT1 and MECP2 at the mRNA level was significantly decreased in GD patients compared with normal controls (p<0.05). Our findings revealed that the DNA methylation pattern in GD was distinct from that of controls. These results provided new molecular insights into the pathogenesis of GD.
authors.affiliation: Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, School of Medical, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China; Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Tian-tian
authors.initials: TT
authors.lastname: Cai
authors.affiliation: Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, School of Medical, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China; Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Fatuma-said
authors.initials: FS
authors.lastname: Muhali
authors.affiliation: Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, School of Medical, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China; Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Rong-hua
authors.initials: RH
authors.lastname: Song
authors.affiliation: Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, School of Medical, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China; Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, School of Medical, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China; Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Liang-feng
authors.initials: LF
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China.
authors.forename: Dan-feng
authors.initials: DF
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Shanghai, 201508, China. Electronic address: zhangjinan@hotmail.com.
authors.forename: Jin-an
authors.initials: JA
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: C573420:ICAM1 protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
keywords: DNA methylation; DNMTs; Graves' disease; ICAM1; MBDs; MeDIP-chip