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

Hum Immunol. 2006 Apr-May;67(4-5):363-73. doi: 10.1016/j.humimm.2006.03.022. Epub 2006 May 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Arthritis, Rheumatoid / genetics*
  • Chronic Disease
  • DNA / chemistry
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Linkage Disequilibrium
  • Nucleic Acid Conformation
  • Polymorphism, Single Nucleotide*
  • Polymorphism, Single-Stranded Conformational*
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA / methods*
  • Takayasu Arteritis / genetics*
  • Transcription, Genetic

Substances

  • Adaptor Proteins, Signal Transducing
  • Histocompatibility Antigens Class II
  • NFKBIL1 protein, human
  • DNA