title: Identification of regulatory polymorphisms in the TNF-TNF receptor superfamily.
abstract: The tumor necrosis factor and TNF receptor (TNF-TNFR) superfamily plays very important roles in the pathogenesis of many immune-mediated diseases. Regulation of TNF-TNFR superfamily gene expression influences many aspects of the pathology associated with these diseases. In order to investigate genetic variations in the regulatory regions of the TNF-TNFR superfamily genes, promoter regions were screened by sequencing DNA samples from 24 unrelated Korean individuals. We identified a total of 68 single-nucleotide polymorphisms (SNPs) in the regulatory regions of the known TNF-TNFR superfamily genes, including 50 SNPs in the promoter regions, 16 SNPs in the 5'-UTR regions, and two SNPs in the coding regions of these genes. Among the 68 SNPs identified in this study, 25 SNPs were novel SNPs. Interestingly, the sequence alteration created by 11 SNPs completely abolished putative transcription factor binding sites in these alleles. These results suggest that these SNP sites can regulate gene expression by controlling the binding of transcription factors. The identification of function-altering SNPs in the promoter regions of the TNF-TNFR superfamily will facilitate efforts to understand the association of TNF-TNFR superfamily genes with several immune-mediated human diseases.
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, Seoul, 122-701, South Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Song-Mean
authors.initials: SM
authors.lastname: Moon
authors.forename: Ha-Jung
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Hung-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.forename: Kuchan
authors.initials: K
authors.lastname: Kimm
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D001665:Binding Sites / Q000235:genetics; D044383:Black People; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007564:Japan; D007723:Korea; D005810:Multigene Family; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics*; D044465:White People
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D048069:Tumor Necrosis Factors; D004247:DNA