Variant Polymorphisms of the IL–1 Receptor Antagonist Gene, IL1RN, Are Underrepresented in an Acute Anterior Uveitis Cohort

Abstract

Abstract: : Purpose: Polymorphisms in the interleukin–1 (IL–1) receptor antagonist gene, IL1RN, have been implicated in various inflammatory diseases. In this study, we examined two IL1RN polymorphisms in a cohort of patients with acute anterior uveitis (AAU), i.e., the phenotype of uveitis commonly associated with the spondyloarthropathies. Methods: All subjects provided informed consent and the protocol was approved by the OHSU IRB. Ophthalmology chart notes were carefully examined to confirm the AAU phenotype. Genomic DNA was extracted from peripheral blood cells using standard techniques. Genotyping was performed by denaturing HPLC (WAVE, Transgenomic Inc., Omaha, NE) and if necessary, verified by direct DNA sequencing. Two IL1RN polymorphisms were genotyped: (i) the single nucleotide polymorphism (SNP) NCBI rs419598, T/C, a silent mutation at amino acid 57 (alanine) in isoform 1 of the IL–1RA protein and (ii) the 86–base pair variable nucleotide tandem repeat (VNTR) in intron 2. Allele frequencies were calculated and compared using the Fisher’s exact test. Results:Twenty–three patients with AAU (11 female, 12 male) and 42 healthy controls (21 female, 21 male) were included in this study. Patients and controls resided in the U.S. or Canada, with the majority of each group from the Pacific Northwest. Both cohorts were predominately Caucasian. The variant rs419598 SNP was present in 31/84 alleles (36.9%) of the controls versus 5/46 alleles (10.9%) of the AAU patients, P = 0.0018. The variant VNTR polymorphism was also found in 31/84 alleles (36.9%) of the healthy controls, and in 8/46 alleles (17.4%) of the AAU cohort, P = 0.0272. Conclusions: Here we show that 2 variant polymorphisms of IL1RN are underrepresented in an AAU cohort compared to matched healthy controls. Menezo et al. observed a similar trend with the rs419598 SNP (referred to as +2018) in patients with chronic anterior uveitis (ARVO 2004 abstract #3717). These results are in contrast to studies which suggest an increased association of variant IL1RN polymorphisms with inflammatory diseases such as systemic lupus erythematosus and ulcerative colitis.

Keywords: inflammation • candidate gene analysis • genetics