CARD15/NOD2 Polymorphisms Do Not Predispose to Acute Anterior Uveitis

Abstract

Purpose:: Approximately 2-9% of patients with inflammatory bowel disease (IBD) will develop uveitis. Polymorphisms in CARD15 (also called NOD2) predispose individuals to a form of IBD known as Crohn’s disease (CD) as well as a rare form of uveitis known as familial juvenile systemic granulomatosis. CARD15 represents up to 20% of the genetic risk to CD which is primarily attributed to 3 non-synonymous polymorphisms (encoding R702W, G908R and 1007 frameshift). In this study we examine these 3 polymorphisms in a cohort of subjects with acute anterior uveitis (AAU) to determine if their presence is associated with AAU.

Methods:: The study was approved by the OHSU IRB and all participants gave informed consent. Individuals diagnosed with AAU were recruited from the uveitis clinic at the Casey Eye Institute and from collaborating physicians in the US, Canada and Germany. The phenotype of AAU was defined as sudden onset, unilateral, anterior uveitis of less than 3 months duration and was carefully documented as such based on ophthalmology records. DNA samples were screened for CARD15 polymorphisms by dHPLC and verified by direct sequencing. Statistical analyses were performed using Fisher’s Exact Test.

Results:: Ninety subjects with confirmed AAU were genotyped (32 male, 58 female, mean age 47, range 13-87). Eighty-nine healthy controls were also genotyped (50 male, 39 female, mean age 50, range 35-85). Ethnicity/racial representation was similar for each group, the majority of subjects being Caucasian. Combined allele frequencies for the 3 tested polymorphisms were not significantly different between the groups (AAU: 11 variant alleles out of 180, and control group: 6 variant alleles out of 178, P=0.32). There were no homozygous individuals and one compound heterozygote (R702W/G908R) in the AAU cohort, while one individual was homozygous for the G908R variant in the control group. Analysis of each polymorphism separately also did not detect any significant differences between the groups.

Conclusions:: CARD15 polymorphisms known to be associated with CD do not appear to be present at a higher frequency in association with AAU compared to healthy controls. The AAU cohort was phenotypically very homogeneous, exhibiting the clinically distinct uveitis presentation typically observed in HLA-B27 associated spondyloarthritis.

Keywords: inflammation • candidate gene analysis • genetics