title: Integrated analyses of a major histocompatibility complex, methylation and transcribed ultra-conserved regions in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which affects different organs and systems that, has a complex genetic inheritance, and is affected by both epigenetic and environmental risk factors. Previous studies on SLE have lacked the statistical power and genetic resolution to fully determine the influence of major histocompatibility complex (MHC) on SLE. In this study, in order to determine this influence, a total of 15 patients with SLE and 15 healthy controls were enrolled. MHC region capture technology, hMeDIP-chip, transcribed ultra-conserved region (T-UCR) microarray and bioinformatics analysis were utilized for both groups. The results revealed methylated CpG enrichment at 6 loci in the MHC segment of SLE. We found 4 single-nucleotide polymorphisms (SNPs) in the CpG promoter of human leukocyte antigen-B (HLA-B) and 2 SNPs in chr6:29521110‑29521833. No significant GO term or KEGG pathway enrichment was noted for an immune-correlated process in the SLE patients for the corresponding CpG-methylated genes. In this study, T-UCR was not discovered in the MHC segment. The analysis of SNPs (rs1050683, rs12697943, rs17881210, rs1065378, rs17184255 and rs16895070) and gene expression in peripheral blood lymphocytes indicated that these SNPs were associated with the occurrence of SLE. Further studies are warranted to examine the roles of these SNPs in the pathogenesis of SLE. Integrative analysis technology provided a view of the molecular signaling pathways in SLE.
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Sui
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Qiupei
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Jiejing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Minglin
authors.initials: M
authors.lastname: Ou
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xue
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Li
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Cuihui
authors.initials: C
authors.lastname: Cao
authors.affiliation: Nephrology Department of 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult