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. 2001 Apr;48(4):461–467. doi: 10.1136/gut.48.4.461

Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians

M Carter 1, G di 1, S Jones 1, J Mee 1, N Camp 1, A Lobo 1, G Duff 1
PMCID: PMC1728235  PMID: 11247888

Abstract

BACKGROUND AND AIMS—An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in intron 2 and ulcerative colitis was first reported in 1994. Subsequent studies in Caucasian Northern European patients have not confirmed this, although trends towards an association were observed. The lack of statistical significance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patients and a meta-analysis of reported patient series was performed.
PATIENTS AND METHODS—A total of 320 patients with endoscopically and histologically confirmed ulcerative colitis (124 pancolitis, 196 left sided and distal disease) and 827 ethnically matched controls were genotyped at polymorphic sites in the interleukin 1 receptor antagonist gene. Carriage rates were compared using χ2 statistics. A meta-analysis of this and seven previous studies in North European Caucasian patients was performed using the Mantel-Haenszel χ2 test.
RESULTS—Patients had a significantly increased carriage rate of allele 2 compared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele 2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio 1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of all eight studies showed a significant association between carriage of allele 2 and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01).
CONCLUSIONS—The association of the interleukin 1 receptor antagonist gene polymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high attributable risk in a population due to the high allelic frequency. Accurate phenotypic characterisation defines more homogeneous subsets of patients, such as those with extensive disease, in whom the association is greater.


Keywords: ulcerative colitis; cytokine gene polymorphisms; interleukin 1 receptor antagonist; interleukin 1; inflammatory bowel disease; genetics

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Figure 1  .

Figure 1  

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Interleukin 1 receptor antagonist gene (IL-1RN) +2018 exon 2 single nucleotide polymorphism genotyping using restriction enzyme digestion of amplified polymerase chain reaction (PCR) products. Lane 1 contains a standard DNA ladder. Lanes 2-7 contain DNA from three individuals. Amplified PCR products from each individual were divided into two aliquots and separately digested with AluI or MspI. PCR products were size fractionated by 9% polyacrylamide gel electrophoresis and visualised under ultraviolet light after staining with ethidium bromide. The two enzymes cut the two alleles differently. AluI cuts the 154 base pair fragment to produce 126 and 28 base pair fragments in allele 1 while it does not digest allele 2 (154 base pairs). MspI digestion produces 125 and 29 base pair fragments in allele 2 but does not digest allele 1 (154 base pairs). Hence the two reactions (separated side by side on a gel) will give inverted patterns of digestion for homozygous individuals (lanes 4/5 and 6/7), and identical patterns in heterozygotes (lanes 2/3).

Figure 2  .

Figure 2  

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Graphic display of individual and summary odds ratios with 95% confidence intervals (CI) for the seven previously published studies of the interleukin 1 receptor antagonist gene (IL-1RN) polymorphism in ulcerative colitis, the present study, and the meta-analysis. Studies are shown as first author with the reference number.

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