Cytokine gene polymorphism in microscopic colitis association with the IL-6-174 GG genotype

Abstract

Microscopic colitis (MC) is a chronic inflammatory disease with unknown pathogenesis. Very little is known about polymorphisms in the cytokine genes in MC. We have investigated the occurrence of well-characterized polymorphisms of interleukins (IL-6, IL-1β, IL-1 receptor antagonist, IL-10) and CD14 in MC. We also determined the serum IL-6 levels. We genotyped 81 patients with MC and 178 controls for polymorphisms of IL-6-174, IL-1β-511, IL-1β-3953, IL-1 receptor antagonist, IL-10-1082 and CD14-159. Serum concentration of IL-6 was measured in 72 patients. Genotype GG of IL-6-174 was more prevalent in MC compared with the controls (P=0.030; odds ratio: 1.941; confidence interval: 1.078-3.495), and the frequency of allele G of IL-6-174 was higher in MC (0.55 vs. 0.47; P=0.036; odds ratio: 1.514; confidence interval: 1.041-2.203). However, after correction for multiple comparisons, the difference became nonsignificant. IL-6 genotype and the serum IL-6 concentration showed no association. The concentration of IL-6 was higher in patients with collagenous colitis than in those with lymphocytic colitis (median 1.73 vs. 1.34 pg/ml, P=0.011). No association between polymorphisms of other cytokine genes and MC was seen. The IL-6-174 gene polymorphism has a possible association with MC, as the IL-6 GG genotype was more frequent in patients with the disease. As this genotype may be linked with an enhanced IL-6 production, we speculate that this polymorphism can influence the pathogenesis of MC by evoking a proinflammatory bias in the mucosal cytokines. The enhanced concentration of IL-6 in collagenous colitis compared with lymphocytic colitis supports a difference in the pathogenetic mechanisms between the two subgroups of MC.