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

Background and aims-An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in i ntron 2 and ulcerative colitis was first reported in 1994. Subsequent studi es in Caucasian Northern European patients have not confirmed this, althoug h trends towards an association were observed. The lack of statistical sign ificance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patie nts and a meta-analysis of reported patient series was performed. Patients and methods-A total of 320 patients with endoscopically and histol ogically confirmed ulcerative colitis (124 pancolitis, 196 left sided and d istal disease) and 827 ethnically matched controls were genotyped at polymo rphic sites in the interleukin 1 receptor antagonist gene. Carriage rates w ere compared using chi (2) statistics. A meta-analysis of this and seven pr evious studies in North European Caucasian patients was performed using the Mantel-Haenszel chi (2) test. Results-Patients had a significantly increased carriage rate of allele 2 co mpared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (C I) 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 sig nificant association between carriage of allele 2 and ulcerative colitis (o dds ratio 1.23 (95% CI 1.04-1.45); p=0.01). Conclusions-The association of the interleukin I receptor antagonist gene p olymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high a ttributable risk in a population due to the high allelic frequency. Accurat e phenotypic characterisation defines more homogeneous subsets of patients, such as those with extensive disease, in whom the association is greater.