Alimentary TractFunctional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis☆,☆☆
Section snippets
Patients treated at LAC-USC Medical Center
Sixty unrelated patients with UC (33 men, 27 women) treated at the clinical IBD Center, Los Angeles County–University of Southern California (LAC-USC) Medical Center, were evaluated. This patient population was 80% Spanish-Caucasian, 15% white-Caucasian, and 5% African-American (Table 1). None of the patients in this study had known Jewish ancestry. The diagnosis of UC was documented by clinical, endoscopic, and histological criteria. Informed consent was obtained from each patient, and the
Patients treated at LAC-USC Medical Center
The carriage rate (number of individuals who have at least 1 copy of the allele) of IL-1RN*2 was increased from 33% in the control population to 70% in the UC group (P < 0.001, Figure 1).
Discussion
Recent studies from our laboratory have provided evidence that insufficient production of the anti-inflammatory cytokine IL-1ra may be an important contributing factor during chronic intestinal inflammation and that an imbalance between IL-1 and IL-1ra may contribute to the pathogenesis of IBD.29 However, the mechanisms of this imbalance are not fully understood.30 In the present study, we attempted to investigate the hypothesis that the amount of IL-1ra an individual can produce is genetically
Acknowledgements
The authors thank Oscar Tejeda and Daniel L. Coulter for their contribution to this work.
References (41)
- et al.
Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews
Gastroenterology
(1989) - et al.
A new syndrome of Crohn's disease and pachydermoperiostosis in a family
Gastroenterology
(1997) - et al.
Distinct associations of HLA class II genes with inflammatory bowel disease
Gastroenterology
(1993) - et al.
Molecularly defined HLA-DR2 alleles in ulcerative colitis and an antineutrophil cytoplasmic antibody–positive subgroup
Gastroenterology
(1995) - et al.
Tumor necrosis factor microsatellites define a Crohn's disease–associated haplotype on chromosome 6
Gastroenterology
(1996) - et al.
Crohn's disease: concordance for site and clinical type in affected family members—potential hereditary influences
Gastroenterology
(1996) - et al.
Clinical characteristics of Crohn's disease in 72 families
Gastroenterology
(1996) - et al.
Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist
Gastroenterology
(1994) - et al.
Ulcerative colitis–like disease in mice with a disrupted interleu-kin-2 gene
Cell
(1993) - et al.
Interleukin-10–deficient mice develop chronic enterocolitis
Cell
(1993)
Genetic aspects of idiopathic inflammatory bowel disease
Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews
Gut
Familial occurrence of inflammatory bowel disease
N Engl J Med
Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking
Gut
Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (anti-neutrophil cytoplasmic antibodies (ANCA) markers
J Clin Invest
An increased risk of Crohn's disease in individuals who inherit the HLA class II DRB3*0301 allele
Proc Natl Acad Sci USA
Ter williger JD, Lathrop GM, Bell JI, Jewell DP. Two stage genomewide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7, and 12
Nat Genet
Mapping of a susceptibility locus for Crohn's disease on chromosome 16
Nature
Susceptibility locus for inflammatory bowel disease on chromosome 16 has a role in Crohn's disease, but not in ulcerative colitis
Hum Mol Genet
Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease
J Immunol
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Address requests for reprints to: Fabio Cominelli, M.D., Ph.D., Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Multistory Building, 2nd Floor, P.O. Box 10033, Charlottesville, Virginia 22906. e-mail: [email protected]; fax: (804) 243-6405.
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Supported by National Institutes of Health grants DK46763, DK43211, DK42191, and DK45740 and the Crohn's and Colitis Foundation of America.