The Cannabinoid 1 Receptor (CNR1) 1359 G/A Polymorphism Modulates Susceptibility to Ulcerative Colitis and the Phenotype in Crohn's Disease

• Published in: PloS one Vol. 5; no. 2; p. e9453
• Main Authors: Storr, Martin, Emmerdinger, Dominik, Diegelmann, Julia, Pfennig, Simone, Ochsenkühn, Thomas, Göke, Burkhard, Lohse, Peter, Brand, Stephan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.02.2010; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Age of Onset; Aged; Aged, 80 and over; Alleles; Analysis; Blood & organ donations; Body mass; Body Mass Index; Cannabinoids; Carriers; Child; Child, Preschool; Colitis; Colitis, Ulcerative - genetics; Colitis, Ulcerative - pathology; Colon; Crohn Disease - epidemiology; Crohn Disease - genetics; Crohn Disease - pathology; Crohn's disease; Crohns disease; Demographics; Deoxyribonucleic acid; Disease susceptibility; DNA; Endocannabinoid system; Female; Gastroenterology and Hepatology; Gastroenterology and Hepatology/Inflammatory Bowel Disease; Gastrointestinal diseases; Gene Frequency; Gene polymorphism; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics and Genomics/Genetics of Disease; Genotype; Genotype & phenotype; Humans; Infant; Infant, Newborn; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Male; Medicine; Mutation; Patients; Phenotype; Physiology; Polymorphism; Polymorphism, Single Nucleotide; Population; Receptor, Cannabinoid, CB1 - genetics; Rodents; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Ulcerative colitis; Young Adult; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009453

Recent evidence suggests a crucial role of the endocannabinoid system, including the cannabinoid 1 receptor (CNR1), in intestinal inflammation. We therefore investigated the influence of the CNR1 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) on disease susceptibility and phenotype in patients with ulcerative colitis (UC) and Crohn's disease (CD). Genomic DNA from 579 phenotypically well-characterized individuals was analyzed for the CNR1 1359 G/A SNP. Amongst these were 166 patients with UC, 216 patients with CD, and 197 healthy controls. Compared to healthy controls, subjects A/A homozygous for the CNR1 1359 G/A SNP had a reduced risk to develop UC (p = 0.01, OR 0.30, 95% CI 0.12-0.78). The polymorphism did not modulate CD susceptibility, but carriers of the minor A allele had a lower body mass index than G/G wildtype carriers (p = 0.0005). In addition, homozygous carriers of the G allele were more likely to develop CD before 40 years of age (p = 5.9x10(-7)) than carriers of the A allele. The CNR1 p.Thr453Thr polymorphism appears to modulate UC susceptibility and the CD phenotype. The endocannabinoid system may influence the manifestation of inflammatory bowel diseases, suggesting endocannabinoids as potential target for future therapies.