Is interleukin-6 important in inflammatory bowel disease?
The IL-6 gene maps to an area of chromosome 7 known to be significant for susceptibility to inflammatory bowel disease. The functional effects of interleukin-6 (IL-6) polymorphisms in the 4th intron and in the 3' flanking region of IL-6 gene were studied in 192 inflammatory bowel disease patients and healthy subjects. A polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to determine a G to A polymorphism (* at position 4470 in intron 4 of IL-6 gene). Four alleles in the 3' flanking region were studied using a variable number of tandem repeats PCR (VNTR-PCR) amplification. Production of IL-6 was measured in lipopolysaccharide (LPS) stimulated whole blood samples by an enzyme-linked immunosorbent assay (ELISA). A modest increase in the frequency of the IL-6*G allele was noted in Crohn's disease (CD) patients (50%) and ulcerative colitis (UC) patients (46.1%) as compared to controls (39.8%, P = 0.025). We were unable to find any significant functional effect of the IL-6 polymorphisms tested on IL-6 protein production. We postulate that the IL-6 polymorphisms investigated here may be in linkage disequilibrium with a susceptibility gene and that they may be utilised as genetic markers.
Koss
K
K
Gastroenterology Unit, Radcliffe Infirmary, Oxford, UK. konradkoss@yahoo.com
Satsangi
J
J
Welsh
K I
KI
Jewell
D P
DP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology*; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017931:DNA Primers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10