(GT)n Dinucleotide repeat polymorphism of haem oxygenase-1 promotor region is not associated with inflammatory bowel disease risk or disease course

Abstract

SummaryHaem oxygenase-1 (HO-1) up-regulation was suggested to reduce mucosal tissue damage in inflammatory bowel disease (IBD) and an up-regulation of HO-1 expression in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated. A HO-1 gene promoter microsatellite (GT)n dinucleotide repeat polymorphism was associated with regulation of HO-1 in response to inflammatory stimuli. We therefore hypothesized that IBD patients might segregate into phenotypes with high or low HO-1 inducibility. Ethylenediamine tetraacetic acid blood samples were obtained from 179 CD patients, 110 UC patients and 56 control patients without inflammation. Genomic DNA was purified and the 5Ј-flanking region of the HO-1 gene containing the (GT)n dinucleotide repeat was amplified. Polymerase chain reaction (PCR) products were purified and the length of the PCR fragments was analysed. The number of (GT)n repeats in the population studied ranged from 13 to 42. The distribution of the allele frequencies was comparable in patients and controls for both the short and the long alleles. The frequencies of short-, middle-and long-sized alleles were not changed among the groups studied. No correlation was found between IBD and microsatellite instability detected in five individals. Our data indicate that (GT)n dinucleotide repeats of the HO-1 promotor region have no significance for the pathophysiology and disease course of IBD.

Haem arginate infusion stimulates haem oxygenase‐1 expression in healthy subjects

“…However, similar statistical results were obtained irrespective of the cut‐off level. The prevalence of the S/S genotype in the cohort under study is in agreement with published data from Austria (Funk et al ., 2004) and Germany (Hausmann et al ., 2008; Lublinghoff et al ., 2009), whereas the prevalence of the S/S genotype seems to be more frequent in Asian populations (17–23 %) (Chen et al ., 2002; 2008; Kaneda et al ., 2002). Previous reports described higher serum bilirubin levels in a large sample of S/S carriers (Endler et al ., 2004; Immenschuh et al ., 2007; Chen et al ., 2008).…”

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

“…The HO-1 A-413T polymorphism has not previously been studied in relation to IBD, whereas no association was found between IBD and HO-1 (GT)N [49]. However, all these studies were small, the largest studies included 500 participants, and thus with limited statistical power to exclude an association.…”

Modulation of Antiviral Immunity by Heme Oxygenase-1

“…20 Depending on the length of the (GT) n repeat, different outcomes are possible. For instance, short (<25) (GT) n repeats significantly up-regulate HO-1 transcription and activity in response to inflammatory stimuli and are associated with a protective phenotype, by reducing the risk of ischemic cerebrovascular events, 21,22 rheumatoid arthritis, 23 or chronic pulmonary emphysema. 24 On the contrary, long (GT) n repeats led to a lower transcriptional activity of HO-1 and have been reported to be associated with higher susceptibility to the development of malignant tumors 25 and coronary artery atherosclerosis.…”