Five genetic markers in the interleukin 1 family in relation to inflammatory bowel disease.
BACKGROUND
An imbalance between the proinflammatory cytokine interleukin 1 beta (IL-1 beta) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has been postulated as a pathogenic factor in inflammatory bowel disease (IBD).


OBJECTIVE
To study allelic frequencies of novel polymorphisms in the genes for IL-1 beta and IL-1ra in patients with IBD and to assess the relation between ex vivo cytokine production and allelic variants of the IL-1 beta and IL-1ra genes.


METHODS
Two hundred and seventy healthy controls, 74 patients with ulcerative colitis (UC), 72 with Crohn's disease (CD), 40 with primary sclerosing cholangitis for the allelic frequencies, and 60 healthy individuals for the ex vivo stimulation test.


METHODS
Genotyping was performed by polymerase chain reaction and subsequent cleavage with specific endonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novel restriction fragment length polymorphisms (RFLPs) in the genes for IL-1ra and IL-1 beta.


RESULTS
No significant differences were found in the allelic frequencies or allele carriage rates of the markers in the IL-1 beta and IL-1ra genes between CD, UC, and healthy controls. No association between the genetic markers and cytokine production levels was observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly more frequently (35.2% in UC versus 71.1% in controls).


CONCLUSIONS
UC is associated with carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs. However, it could not be confirmed whether the association reflects a pathogenic mechanism underlying UC.
Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
P C
PC
Stokkers
B E
BE
van Aken
N
N
Basoski
P H
PH
Reitsma
G N
GN
Tytgat
S J
SJ
van Deventer
D000328:Adult; D000704:Analysis of Variance; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000276:immunology; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012044:Regression Analysis
D005819:Genetic Markers; D007375:Interleukin-1; D017472:Receptors, Interleukin-1