Interferon–Gamma Polymorphisms as Genetic Predictors of Uveitis in Sarcoidosis

Abstract

Abstract: : Purpose: Cytokines are known to play an important role in the pathogenesis and disease progression of sarcoidosis and high levels of Interferon–Gamma have been found in patients with pulmonary disease. The aim of this study was to determine if any correlation exists between Interferon–Gamma (IFN–γ) and Interferon–Gamma Receptor 1 (IFN–γ–R1) polymorphisms and associated uveitic involvement in patients with sarcoidosis. Methods: 120 UK Caucasian patients with systemic sarcoidosis were identified and subdivided into 2 categories: 39 with associated uveitis and 81 without; 55 age–matched patients with idiopathic uveitis were used as a control. Total genomic DNA from peripheral citrated blood was extracted using a salt extraction method and four separate IFN–γ and two separate IFN–γ–R1 polymorphisms were identified using TaqMan PCR. Results: We compared the phenotype, genotype and allele distributions of each of the groups for each of the six polymorphisms in turn, looking for statistically significant differences. We found a significant difference in the frequency of IFN–γ (–4925) C/T genotype in the group of patients with systemic sarcoidosis and associated uveitis compared to those without eye involvement (95% vs. 80%, p = 0.01). There was a trend in the genotype frequency of IFN–γ (–2671) T/C and IFN–γ (–2459) A/G in patients with sarcoidosis and inflammatory eye disease compared to those with no eye involvement [(77% vs. 70%, p = 0.07) and (82% vs. 72%, p = 0.09) respectively]. Conclusion: In this preliminary study we found a statistically significant difference between phenotype and the IFN–γ (–4925) C/T genotype, and a trend in the distribution of the IFN–γ (–2671) T/C and IFN–γ (–2459) A/G genotypes. This limited success may represent the relatively small number of known IFN–γ and IFN–γ–R1 polymorphisms that were examined, the influence of cytokines such as IL–12 and IL–18 on IFN–γ production rather than intrinsic IFN–γ polymorphisms or may represent the fact that the groups of patients examined were at different stages of disease progression. These possible explanations provide direction for further study.

Keywords: uveitis–clinical/animal model • cytokines/chemokines • genetics