Association of the haem oxygenase-1 gene with inflammatory bowel disease

Abstract

The anti-inflammatory genes, haem oxygenase 1 (HO-1, HMOX1) rs2071746 (unrestricted model: p = 9.07 × 10-4; recessive model: p = 4.99 × 10-4; multiplicative model: p = 0.0009; and additive model: p = 1.87 × 10-4) and interleukin-10 (IL-10) rs1800872 (dominant model: p = 0.0277) have been associated with paediatric inflammatory bowel disease. The present family-based case-trio study (n = 52) examined HO-1 gene expression in the presence of proinflammatory lipopolysaccharide and tumour necrosis factor-alpha in four B lymphocyte cell lines established from children with inflammatory bowel disease and demonstrated that mutations in IL-10 and IL-10 receptor B reduced HO-1 messenger RNA expression. This observation supports our hypothesis that HO-1 is regulated by the IL-10/ STAT3 pathway and that both genes (IL10 and STAT3) could be involved in the pathogenesis of inflammatory bowel disease. We also compared HO-1 expression in diseased intestinal tissues with adjacent normal tissues from adults with inflammatory bowel disease. Of the 17 Crohn’s disease patients, HO-1 expression in diseased tissues was downregulated in 9 patients (53%) and of the 10 ulcerative colitis patients HO-1 was downregulated in 7 patients (70%), compared with adjacent normal tissues. The downregulation of HO-1 gene expression may lower anti-inflammatory effects and worsen tissue injury in affected areas by inflammatory bowel disease.