Polymorphism in the Retinoic Acid Metabolizing Enzyme CYP26B1 and the Development of Crohn’s Disease

Abstract

Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn’s disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.

Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

“…They individually affect the metabolism of drugs or endogenous compounds. Little is known with respect to carotenoids, but it was shown that a polymorphism regarding CYP26B1 (rs2241057) influences the degradation of retinoic acid, and is likely related to the risk of Crohn's disease and atherosclerosis .…”

Supernumerary teeth in the pharyngeal dentition of slow-developing zebrafish (Danio rerio , Hamilton, 1822)

“…() reported the presence of an additional tooth in the ventral row, posterior to the tooth position 5V, in wild‐type zebrafish ( cyp 26b1 +/+) treated with all‐trans retinoic acid, and for the heterozygous adult zebrafish mutant stocksteif ( sst ) ( cyp 26b1 +/−). The gene cyp 26b1 encodes for an enzyme involved in the degradation of retinoic acid (Fransén et al., ) and thus the zebrafish mutant stocksteif possesses dentitions similar to wild‐type zebrafish treated with exogenous retinoic acid. The digitalized microtomography image of the dentition of an adult stocksteif mutant, shown in the article, indeed reveals a supernumerary tooth in the ventral row, albeit that the tooth is located anterior to 1V, not posterior to 5V.…”

Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes

“…A polymorphic variation rs2241057C/C (minor allele) L264S is associated with larger macrophage-positive atherosclerotic lesions, whereas carries of the major allele rs2241057T/T have an increased risk of Crohn's disease, an autoimmune condition of the gut. Additionally, Cyp26b1 is upregulated in atheroschlerotic lesions and associated there with activated macrophages, suggesting that Cyp26b1 may be important in RA clearance in the arterial wall [215][216][217]. Neural tube, limb, craniofacial, skeletal, heart, kidney and lung defects [207] (samples collected during gestation) Several papers have reported human skeletal abnormalities in patients with CYP26B1 mutations.…”