title: Direct determination of single nucleotide polymorphism haplotype of NFKBIL1 promoter polymorphism by DNA conformation analysis and its application to association study of chronic inflammatory diseases.
abstract: We previously revealed that one of the human leukocyte antigen-linked susceptibility genes for Takayasu's arteritis (TA) was mapped between TNFA and MICB loci and that -63T allele of NFKBIL1, which is between TNFA and MICB loci, was associated with rheumatoid arthritis (RA) in the Japanese population. We have developed a novel typing method based on reference strand-mediated conformation analysis for the upstream sequence of the NFKBIL1 gene, where -422 (T)8/(T)9, -325 C/G, -263 A/G, and -63 T/A polymorphisms were found. Upon the analysis of the patients with TA (n = 84), those with RA (n = 120), and healthy control subjects (n = 217), five common haplotypes named IKBLp*01 through IKBLp*05 were found in the Japanese population. The frequency of IKBLp*03 was significantly increased in the patient with TA (57.1% vs 35.0%, giving an odds ratio of 2.47). In addition, the frequency of IKBLp*01, but not that of other -63T-bearing alleles, was increased in the patients with RA (73.3% vs 58.1%, giving an odds ratio of 1.99), suggesting that the susceptibility to RA was conferred not by -63T alone but by combination of single nucleotide polymorphisms in the NFKBIL1 promoter. A higher promoter activity associated with IKBLp*03 and a lower activity associated with IKBLp*01 may contribute to the susceptibility to TA and RA, respectively.
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Obuchi
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Fujio
authors.initials: F
authors.lastname: Numano
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002908:Chronic Disease; D004247:DNA / Q000737:chemistry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D013625:Takayasu Arteritis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human; D004247:DNA