Chemokine Genes Polymorphisms in Posterior Non–Infectious Uveitis

Abstract

Abstract: : Purpose: CC chemokines are important chemo attractants for Th1 cells that play crucial role in uveitis. Single nucleotide polymorphisms at promoter sites of CCL2 –2518, CCL5 –403, CCL5 –28 and CCR5 –59029 effect the expression of the respective genes and are found to be associated with various Th1 mediated autoimmune diseases. Similarly 32bp deletion in CCR5 gene and V64I polymorphism in CCR2 gene have been associated with autoimmune diseases. The aim of this study was to determine any association of these polymorphisms with disease susceptibility, clinical course and response to treatment in patients with non–infectious posterior segment intraocular inflammation. Methods: 205 Caucasian patients with posterior segment non–infectious intraocular inflammation and 283 ethnically matched healthy controls were recruited for this study. Depending upon site and cause of inflammation, the patients were divided into six groups namely, idiopathic intermediate uveitis, sarcoid uveitis, Behcet’s uveitis, vasculitis, posterior uveitis and pan uveitis. Genotyping for CCL2 –2518A/G, CCL5 –403G/A, CCL5 –28C/G, CCR2 V64I, CCR5 –59029 and CCR5 32bp deletion was performed by single specific primer polymerase chain reaction. Genotype distribution between the groups was compared by chi square test. Non parametric tests were used to compare the means of continuous variables between the genotypes. Results: The frequency of CCR5–64I allele was significantly more in the patients as compared to controls (p=0.02). The 64I allele was more common in patients with Behcet’s related uveitis (p=0.006). No significant association was found between other polymorphisms and posterior uveitis, however patients with CCL5 –403A allele develop less severe inflammation as compared to patients with G allele (p=0.04) and final visual outcome was better in patients having CCR5 32bp deletion as compared to patients with wild type allele (p=0.04). Conclusions: CCR2 64I mutation could increase the risk of posterior segment intra–ocular inflammation particularly in patients with behcet’s disease. CCL5 –403 and CCR5 32bp deletion polymorphisms could be predictors of disease severity in patients with non–infectious posterior segment inflammation.

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