Analysis of Crohn’s Disease‐Related CARD15 Polymorphisms in Spanish Patients with Idiopathic Uveitis

Abstract

We wished to analyse the frequency of Crohn’s disease-linked CARD15 polymorphisms (P268S, R702W, G908R and 1007fs) in a group of Spanish patients with idiopathic uveitis. To this aim, DNA samples were obtained from 111 unrelated patients. P268S, R702W and G908R polymorphisms were detected using TaqMan Genotyping kits (Applied Biosystems), and the 1007fs variation by direct DNA sequencing. Control group consisted of 105 healthy subjects.None of the polymorphisms studied revealed a significant increase in the groups of patients, when compared to the control group. Thus, P268S is found in 50% of patients (gene frequency 0.284) vs 44% of control individuals (gene frequency 0.245); R702W in 7% of patients (0.036) vs 7% (0.033); G908R in 2% of patients (0.009) vs 4% (0.019) and, finally, 1007fs in 2% of uveitis patients (0.008) vs 4% (0.021). Moreover, DNA sequencing has allowed us to define two new intronic polymorphisms in phase, in the 5' and 3' boundaries of the exon 11 (GenBank accession number #DQ 869189). Altogether, our results suggest that the Crohn’s disease-linked CARD15 polymorphisms do not seem to predispose to idiopathic uveitis in the Spanish population.

Blau Syndrome-Related CARD15/NOD2 Mutations Are Not Linked to Idiopathic Uveitis in Spanish Patients

“…However, other inflammatory conditions that show no or weak CARD15 association, such as ulcerative colitis [9], rheumatoid arthritis, ankylosing spondylitis, type I diabetes or systemic lupus erythematosus [5] lack this clinical feature. We further report here on another inflammatory condition (idiopathic uveitis) that, in most instances (and definitely in none of our patients), is not associated to granuloma formation [4,8] and that also fails to show any association with this gene, whether we analyze the NBD domain (as in the present work) or the LRR region of the molecule (as in a previous work from our group [14]). Some other pathologies, such as malignancies [5] or graft versus host (GvH) disease in stem cell transplantation [3] have been effectively linked to CARD15 mutations and yet none of them is granulomatous.…”

“…A more detailed description of this cohort of patients is given in a previous publication from our group [14]. Written consent was obtained from the all patients involved in this study.…”

The common NOD2/CARD15 variant P268S in patients with non-infectious uveitis: a cohort study

“…In contrast to previous reports [ 11 , 12 ], our study, showed a statistical association between the variant P268S/SNP5 (SNP rs2066842) and ACU, both idiopathic and associated with other rheumatic disease. In our cohort the incidence of variations was not significantly different between our patients with idiopathic chronic uveitis and those with chronic uveitis associated to auto-immune diseases.…”

“…The role of NOD2/CARD15 gene as a key regulator of innate immunity in the eye has been elucidated by studies performed on murine models,which are knockout for NOD2/CARD15, which showed an increased susceptibility to uveitis [ 9 , 10 ]. However the first reports conducted on patients affected by idiopathic uveitis has failed to demonstrate a role for this gene in this disease; two studies conducted on a large cohort of spanish patients with idiopathic uveitis suggested that NOD2/CARD15 variants do not seem to predispose to thee disease [ 11 , 12 ]. In order to investigate the possible role of this gene in ACU, we have studied NOD2/CARD15 variants and the genotype-phenotype correlation in a cohort of patients with idiopathic uveitis and uveitis associated with other inflammatory diseases.…”