Article Text

Download PDFPDF
Linkage of Crohn’s disease-related serological phenotypes: NFKB1 haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF-κB activation
  1. H Takedatsu1,
  2. K D Taylor2,
  3. L Mei2,
  4. D P B McGovern1,
  5. C J Landers1,
  6. R Gonsky1,
  7. Y Cong3,
  8. E A Vasiliauskas1,
  9. A Ippoliti1,
  10. C O Elson3,
  11. J I Rotter2,
  12. S R Targan1
  1. 1
    Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
  2. 2
    Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
  3. 3
    Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, Alabama, USA
  1. Dr S R Targan, Division of Gastroenterology, Inflammatory Bowel Disease Center and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Suite D4063, Los Angeles, CA 90048, USA; targans{at}


Background and aims: Genetics studies of the serum expression of antibodies to microbial antigens may yield important clues to the pathogenesis of Crohn’s disease. Our aim was to conduct a linkage study using expression of anti-CBir1, anti-I2, anti-OmpC and ASCA as quantitative traits.

Methods: Expression of antibodies to microbial antigens was measured by enzyme-linked immunosorbant assay (ELISA) and a standard ∼10 cM whole genome microsatellite study was conducted. Single nucleotide polymorphism genotyping was performed using either Illumina or TaqMan MGB technology. Nuclear factor Kappa B (NF-κB) activation in cells from Epstein–Barr virus (EBV)-transformed cell lines was assessed using an electrophoretic mobility shift assay and protein was measured using ELISA and western blotting.

Results: Evidence for linkage to anti-CBir1 expression was detected on human chromosome 4 (logarithm of odds (LOD) 1.82 at 91 cM). We therefore directly proceeded to test the association of haplotypes in NFKB1, a candidate gene. One haplotype, H1, was associated with anti-CBir1 (p = 0.003) and another, H3, was associated with ASCA (p = 0.023). Using cell lines from Crohn’s disease patients with either H1 or H3, NF-κB activation and NF-κB p105 and p50 production were significantly lower for patients with H1 compared to patients with H3.

Conclusions: These results suggest that NFKB1 haplotypes induce dysregulation of innate immune responses by altering NF-κB expression. The results also show the use of EBV-transformed lymphoblastoid cell lines to conduct phenotypic studies of genetic variation.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding: Supported by USPHS Grants PO1DK071176 and PO1DK046763, the Feintech Chair in Inflammatory Bowel Disease (SRT) and the Cedars-Sinai Board of Governor’s Chair in Medical Genetics (JIR). Genotyping was supported in part by M01-RR00425 to the Cedars-Sinai GCRC genotyping core (KDT).

  • Competing interests: None.

  • Ethics approval: Ethics approval for the study was given by the Cedars-Sinai Institutional Review Board on 1 January 2008.