A Craggs1, S West, A Curtis, M Welfare, M Hudson, P Donaldson, J Mansfield. 1. Depts. of Gastroenterology & Hepatology and Human Genetics and Centre for Liver Research, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK. Alison.Craggs@ncl.ac.uk
Abstract
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract of unknown aetiology, phenotypically categorized into ulcerative colitis (UC) and Crohn disease (CD). Genetic factors are of considerable importance in both. The genetic relationship between IBD and the interleukin-1 receptor antagonist and interleukin-1beta genes (IL-1RN, and IL-1B, respectively) has been extensively studied. However, the quality and outcome of the genetic association studies, in particular the association with IL-1RN*2, have been variable and these associations remain controversial. The aim of the present study was to re-investigate these two candidate genes in a large series of IBD patients from a genetically homogeneous population with low levels of population admixture, and provide a definitive answer to this question. METHODS: A total of 529 northern European Caucasoid patients with IBD (347 UC, 182 CD) and 289 racially and geographically matched healthy controls were studied. The IL-1RN and IL-1B genotypes, allele frequencies and most probable haplotypes were determined by standard PCR protocols. RESULTS: There were no significant differences in the distributions of the IL-1RN and IL-1B genotypes, allele frequencies or haplotypes in either patient series compared to healthy controls or between clinical subsets. Genotype distribution and frequency data for allele 2 (IL-1RN*2) in particular showed no significant differences across all patient groups for all three series. CONCLUSION: The findings of this study lead us to reject the IL-1RN*2 association with IBD.
BACKGROUND:Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract of unknown aetiology, phenotypically categorized into ulcerative colitis (UC) and Crohn disease (CD). Genetic factors are of considerable importance in both. The genetic relationship between IBD and the interleukin-1 receptor antagonist and interleukin-1beta genes (IL-1RN, and IL-1B, respectively) has been extensively studied. However, the quality and outcome of the genetic association studies, in particular the association with IL-1RN*2, have been variable and these associations remain controversial. The aim of the present study was to re-investigate these two candidate genes in a large series of IBD patients from a genetically homogeneous population with low levels of population admixture, and provide a definitive answer to this question. METHODS: A total of 529 northern European Caucasoid patients with IBD (347 UC, 182 CD) and 289 racially and geographically matched healthy controls were studied. The IL-1RN and IL-1B genotypes, allele frequencies and most probable haplotypes were determined by standard PCR protocols. RESULTS: There were no significant differences in the distributions of the IL-1RN and IL-1B genotypes, allele frequencies or haplotypes in either patient series compared to healthy controls or between clinical subsets. Genotype distribution and frequency data for allele 2 (IL-1RN*2) in particular showed no significant differences across all patient groups for all three series. CONCLUSION: The findings of this study lead us to reject the IL-1RN*2 association with IBD.
Authors: Maria Dobre; Elena Milanesi; Teodora Ecaterina Mănuc; Dorel Eugen Arsene; Cristian George Ţieranu; Carlo Maj; Gabriel Becheanu; Mircea Mănuc Journal: J Immunol Res Date: 2018-10-17 Impact factor: 4.818