Analysis of inflammation- and atherosclerosis-related gene polymorphisms in branch retinal vein occlusion

PURPOSE Branch retinal vein occlusion (BRVO) is a common vision-threatening disease. Compression of the underlying retinal vein due to increased rigidity of the crossing artery has been implicated in the pathogenesis of BRVO. Among others, arterial hypertension and hypercholesterolemia, both of which contribute to atherogenesis, have been identified as risk factors. Atherosclerosis itself is a chronic low-grade inflammatory disease with a distinct pro-inflammatory cytokine pattern. In addition to their role in atherogenesis, some cytokines have been shown to exert procoagulatory effects, and may thus contribute to the development of BRVO by a second mechanism. Gene polymorphisms affecting the expression of inflammation-related cytokines are therefore candidates as potential risk factors for BRVO. The purpose of the present study was to investigate hypothesized associations between cytokine gene polymorphisms and the presence of BRVO. METHODS The study comprised 398 patients with BRVO and 355 control subjects. Using 5'exonuclease assays (TaqMan), genotypes of the following functional single nucleotide polymorphisms were determined: interleukin 1 beta (IL1B) -511C>T, interleukin 1 receptor antagonist (IL1RN) 1018T>C, interleukin 4 (IL4) -584C>T, interleukin 6 (IL6) -174G>C, interleukin 8 (IL8) -251A>T, interleukin 10 (IL10) -592C>A, interleukin 18 (IL18) 183A>G, tumor necrosis factor (TNF) -308G>A, monocyte chemoattractant protein 1 (CCL2) -2518A>G, and RANTES (CCL5) -403G>A. RESULTS Neither genotype distributions nor allele frequencies of any of the investigated polymorphisms differed significantly between BRVO patients and controls (p>0.05). Arterial hypertension was found to be significantly more prevalent in BRVO patients than in controls (p<0.001). In a logistic regression analysis presence of arterial hypertension was associated with an odds ratio of 3.33 (95% confidence interval: 2.42-4.57) for BRVO. CONCLUSIONS As none of the investigated gene variants was significantly more prevalent in BRVO patients than among control subjects, our data suggest that these polymorphisms themselves are unlikely major risk factors for BRVO.