title: Functional variant in the promoter region of IL-27 alters gene transcription and confers a risk for ulcerative colitis in northern Chinese Han.
abstract: Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown etiology and a polygenic disease. IL-27 encodes p28, a subunit of IL-12 family cytokines, and has been implicated in the pathogenesis of UC. The aims of the present study were to evaluate the genetic association of a variant of the IL-27 gene with UC and to further characterize the functional variant in the IL-27 gene that influences the risk for UC. Our data demonstrated that the genetic variant rs153109 in the 5' upstream region of IL-27 is significantly associated with UC in Chinese Han individuals. Analysis of IL-27 transcripts demonstrated that individuals carrying the risk allele of rs153109 display reduced transcription of IL-27 in PBMCs. Luciferase activity assays demonstrated that the risk allele rs153109 results in decreased promoter activity compared to a non-risk allele in a tissue specific manner. Mechanistic characterization of histone modifications in the promoter region revealed that the risk haplotype tagged by the risk allele of rs153109 reduces the levels of H3K3me3 and H3K27ac.
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: The Research Center, The Second Hospital of Jilin University, 130041, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun 130041, China. Electronic address: jlfjlu@126.com.
authors.forename: Lifang
authors.initials: L
authors.lastname: Jin
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002681:China; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D042421:Histone Code / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D007378:Interleukins; C464565:MYDGF protein, human
keywords: Gene expression; Genetic association; IL-27; Ulcerative colitis