title: Exploring Genome-wide DNA Methylation Profiles Altered in Kashin-Beck Disease Using Infinium Human Methylation 450 Bead Chips.
abstract: To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high-resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome-wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an 710061, Shannxi, China.
authors.forename: Xiao Wei
authors.initials: XW
authors.lastname: Shi
authors.affiliation: Department of Oncosurgery, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an 710061, Shannxi, China.
authors.forename: Bo Hui
authors.initials: BH
authors.lastname: Shi
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, Xi'an 710061, Shannxi, China.
authors.forename: Ai Li
authors.initials: AL
authors.lastname: Lyu
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, Xi'an 710061, Shannxi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, Xi'an 710061, Shannxi, China.
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Zhou
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, Xi'an 710061, Shannxi, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D057767:Kashin-Beck Disease / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis