TheIL-10 gene is not involved in the predisposition to inflammatory bowel disease

Abstract

Although genetic predisposition for inflammatory bowel disease (IBD) is well established, little is known about the accountable genes. The pathogenesis of IBD is characterized by an imbalanced activation of Th1- and Th2-lymphocytes. IL-10 represents an anti-inflammatory cytokine which downregulates the production of Th1-derived cytokines. To evaluate the role of the IL-10 gene in IBD, two polymorphisms in the promoter region (G/A at position -1082 and C/A at position -592) were genotyped in 142 patients with Crohn's disease (CD), 104 patients with ulcerative colitis (UC), and 400 healthy controls. Significant differences were not apparent, neither in the allele frequencies of either polymorphism, nor in the haplotype frequencies. Screening of the coding region of the IL-10 gene by polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) analysis revealed a rare sequence variation in exon 1 leading to an amino acid exchange (G-->A; G15R) in two patients with CD and five healthy controls. Therefore, polymorphisms of the IL-10 gene are not demonstrably involved in the predisposition of IBD in our cohorts of patients.

Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the –174 IL-6 G/C polymorphism in children

“…Also, we demonstrate that the genetic basis for the variation in height is distinct from that causing a susceptibility to Crohn's disease. The IL-6 -174 genotype conferred no propensity toward developing the disease, confirming other work describing a lack of association of the IL-6 gene with Crohn's disease (51). This effect of the IL-6 promoter is in marked contrast to polymorphisms in the NOD-2 gene which are increased in Crohn's disease (52,53), yet do not affect growth (54).…”

The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study

“…Furthermore, they found no association between the three IL-10 promoter polymorphisms and risk of UC (results regarding CD were not reported). Previous studies were unable to find association between IBD and the IL-10 promoter polymorphisms [22,31,35,39,40] whereas other studies have found associations between paediatric onset of CD and IL-10 C-819T wildtype allele [30], Crs2222202T variant allele [30] and between the IL-10 G-1082A variant allele and risk of UC [58] (Table 4). …”

“…They are in tight linkage disequilibrium [32] and the haplotype encompassing these three polymorphisms is associated with low IL-10 protein production in lymphocytes in vitro [32] and low of levels of circulating IL-10 protein in Kenyan children [33] probably because the A allele of the IL-10 promoter polymorphism C-592A leads to the formation of a binding site for the ETS family of transcription factors [34]. Studies on the IL-10 promoter polymorphisms and IBD susceptibility have been inconsistent [22,29-31,35-40]. …”