Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn's disease in a British population.
Interleukin-4 (IL-4) is an important cytokine in mucosal immunity and plays a critical role in the development of colitis in T-alpha cell receptor mutant mice. Functionally significant polymorphisms have been described in the genes encoding IL-4 and IL-4 receptor. To examine the role of these polymorphisms in disease susceptibility 98 patients with ulcerative colitis, 86 patients with Crohn's disease and 321 healthy controls were genotyped for polymorphisms at position -34 in the IL-4 gene and codon 576 in the IL-4 receptor gene. Thirty-two percent of patients with Crohn's disease carried one or two copies of the variant allele for IL-4 compared with 16% of the controls (P = 0.002). Forty-one percent of patients with Crohn's disease carried one or two copies of the variant IL-4 receptor allele compared with 31% of the controls (P = 0.09). Fifteen percent of patients with Crohn's disease carried combination of both (IL-4 and IL-4 receptor) variant alleles compared with 4% of the controls (P = 0.005). Association with alleles resulting in high IL-4 transcription and enhanced signalling activity suggests that IL-4 may have a role in the pathogenesis of Crohn's disease.
Aithal
G P
GP
Centre for Liver Research, Medical School, University of Newcastle upon Tyne, UK. aithalg@musc.edu
Day
C P
CP
Leathart
J
J
Daly
A K
AK
Hudson
M
M
D001483:Base Sequence; D003424:Crohn Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
D017931:DNA Primers; D019948:Receptors, Interleukin-4; D015847:Interleukin-4