IDO1 and IDO2 Non-Synonymous Gene Variants: Correlation with Crohn's Disease Risk and Clinical Phenotype
Year: 2014
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Genetic polymorphisms can confer CD risk and influence disease phenotype. Indoleamine 2,3 dioxygenase-1 (IDO1) is one of the most over-expressed genes in CD and mediates potent anti-inflammatory effects via tryptophan metabolism along the kynurenine pathway. We aimed to determine whether non-synonymous polymorphisms in IDO1 or IDO2 (a gene paralog) are important either as CD risk alleles or as modifiers of CD phenotype. METHODS: Utilizing a prospectively collected database, clinically phenotyped CD patients (n = 734) and non-IBD controls (n = 354) were genotyped for established IDO1 and IDO2 non-synonymous single nucleotide polymorphisms (SNPs) and novel genetic variants elucidated in the literature. Allelic frequencies between CD and non-IBD controls were compared. Genotype-phenotype analysis was conducted. IDO1 enzyme activity was assessed by calculating the serum kynurenine to tryptophan ratio (K/T). RESULTS: IDO1 SNPs were rare (1.7% non-IBD vs 1.1% CD; p = NS) and not linked to Crohn's disease diagnosis in this population. IDO1 SNPs did however associate with a severe clinical course, presence of perianal disease, extraintestinal manifestations and a reduced serum K/T ratio during active disease suggesting lower IDO1 function. IDO2 minor allele variants were common and one of them, rs45003083, associated with reduced risk of Crohn's disease (p = 0.025). No IDO2 SNPs associated with a particular Crohn's disease clinical phenotype. CONCLUSIONS: This work highlights the functional importance of IDO enzymes in human Crohn's disease and establishes relative rates of IDO genetic variants in a US population.
Source: PLoS ONE
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: IDO1 IN THE HUMAN GUT EPITHELIUM, G1625195244, G1901487210, G444632500, G4764157706, G625676284, Human MAIT celis in airway mucosal immune responses to intracellular infections, Influence of Somatization on Central Pain Responses in Irritable Bowel Syndrome, G8404679437, G8888553755, G9000006413, G9000045851, G9000063635, G9000190148
OpenAlex ID: W2018318066