Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-21
pubmed:abstractText
Association studies have identified the interleukin-1 receptor antagonist gene allele 2(IL-1RN*2) as a marker of susceptibility in ulcerative colitis (UC). This study investigated the significance of the IL-1RN genotype with respect to protein and mRNA expression in the colonic mucosa. Homogenates of rectal biopsies from 99 UC and 54 controls were assayed for cytokines IL-1ra, IL-1a and IL-1b using ELISA. IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis. The ability of the two IL1RN alleles to generate steady-state mRNA accumulation was assessed in the colonic mucosa of seven heterozygous patients. Stepwise linear regression demonstrated that IL-1RN genotype (P=0.001), diagnosis (P<0.0001) and treatment (P<0.03) were independent factors associated with the IL-1ra protein level whilst IL1RN genotype (P=0.005) and macroscopic inflammatory grade (P<0.0001) were associated with the IL-1ra/ total IL-1 ratio. The IL1RN*2 correlated with reduced IL-1ra and IL-1ra/IL-1 ratio with a gene dosage effect. In heterozygous UC patients the ratio of allele 1 mRNA / allele 2 steady state mRNA was always greater than 1 (range: 1.2-3.1) (P=0.018). The IL-1RN*2 is associated with reduced levels of IL-1ra protein and IL-1RN mRNA in the colonic mucosa, providing a biologically plausible explanation for the observed association of the allele with the disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1466-4879
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14735144-3' Untranslated Regions, pubmed-meshheading:14735144-Adolescent, pubmed-meshheading:14735144-Adult, pubmed-meshheading:14735144-Aged, pubmed-meshheading:14735144-Aged, 80 and over, pubmed-meshheading:14735144-Alleles, pubmed-meshheading:14735144-Child, pubmed-meshheading:14735144-Colitis, Ulcerative, pubmed-meshheading:14735144-DNA, Complementary, pubmed-meshheading:14735144-Female, pubmed-meshheading:14735144-Genotype, pubmed-meshheading:14735144-Humans, pubmed-meshheading:14735144-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:14735144-Interleukin-1, pubmed-meshheading:14735144-Intestinal Mucosa, pubmed-meshheading:14735144-Male, pubmed-meshheading:14735144-Middle Aged, pubmed-meshheading:14735144-Polymorphism, Genetic, pubmed-meshheading:14735144-RNA, Messenger, pubmed-meshheading:14735144-Sialoglycoproteins
pubmed:year
2004
pubmed:articleTitle
Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis.
pubmed:affiliation
The Gastroenterology and Liver Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK. Martyn.J.Carter@btinternet.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't