Purpose: To study genetic predispositions and differences between severe chronic central serous chorioretinopathy (cCSC), nonsevere cCSC, and acute central serous chorioretinopathy (aCSC). Methods:... Show morePurpose: To study genetic predispositions and differences between severe chronic central serous chorioretinopathy (cCSC), nonsevere cCSC, and acute central serous chorioretinopathy (aCSC). Methods: One hundred seventy-three severe cCSC patients, 272 nonsevere cCSC patients, 135 aCSC patients, and 1,385 control individuals were included. Eight single-nucleotide polymorphisms were genotyped in theARMS2(rs10490924),CFH(rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), andNR3C2(rs2070951). Additionally,C4Bgene copy numbers were analyzed. Results: A significant association in 5 single-nucleotide polymorphisms in theCFHgene could be reproduced among severe cCSC patients, including rs800292 (P= 0.0014; odds ratio [OR] = 1.93; 95% confidence interval [CI] = 1.51-2.47), rs1065489 (P= 2.22 x 10(-4); OR = 0.49; 95% CI = 0.34-0.72), rs1329428 (P= 0.001; OR = 1.89; 95% CI = 1.49-2.40), rs2284664 (P= 1.21x 10(-4); OR = 1.65; 95% CI = 1.28-2.13), and rs3753394 (P= 6.10x 10(-4); OR = 0.61; 95% CI = 0.46-0.81). Carrying threeC4Bcopies was protective for severe cCSC (P= 0.001; OR = 0.29; 95% CI = 0.14-0.61). No significant differences in allele frequencies could be found among the CSC phenotypes. Conclusion: Acute CSC, nonsevere cCSC, and severe cCSC all showed a similar association with theCFHandC4Bgenes, and the three phenotypes could not be distinguished based on the genetics. This shows that despite the differences in clinical presentation and severity, there is an overlap in the genetic predisposition of different CSC phenotypes. Nongenetic factors may play a more important role in determining the clinical course of CSC. Show less
PURPOSE. To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes.METHODS. We included 797 patients with AMD... Show morePURPOSE. To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes.METHODS. We included 797 patients with AMD and 945 controls from the European Genetic Database. Patients were grouped into five AMD stages: early AMD, intermediate AMD, central geographic atrophy, active choroidal neovascularization or inactive choroidal neovascularization. Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. Differences in complement activation between stages were evaluated stratifying by complement associated haplotypes.RESULTS. Complement activation levels differed significantly between AMD disease stages. As compared with controls, the C3d/C3 ratio was higher in patients with intermediate AMD (P < 0.001) and central geographic atrophy (P = 0.001). Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. The association between AMD disease stage and complement activation was more pronounced in patients with haplotypes associated with the highest complement activation.CONCLUSIONS. In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. Prospective studies are needed to confirm these results. Show less
Hosoda, Y.; Miyake, M.; Schellevis, R.L.; Boon, C.J.F.; Hoyng, C.B.; Miki, A.; ... ; Tsujikawa, A. 2019
Purpose: To investigate genetic associations in white patients with acute central serous chorioretinopathy (aCSC) and to assess genetic differences between aCSC and chronic CSC (cCSC).Methods: A... Show morePurpose: To investigate genetic associations in white patients with acute central serous chorioretinopathy (aCSC) and to assess genetic differences between aCSC and chronic CSC (cCSC).Methods: A total of 135 aCSC patients, 272 cCSC patients, and 1,385 control individuals were included. Eight single nucleotide polymorphisms were genotyped for ARMS2 (rs10490924), CFH (rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), and NR3C2 (rs2070951). Also, C4B gene copy numbers were analyzed.Results: Three single nucleotide polymorphisms in the CFH gene were significantly associated with aCSC: rs800292 (P = 0.003, odds ratio = 1.53 [95% confidence interval = 1.15-2.03]), rs1061170 (P = 0.002, odds ratio = 0.64 [95% confidence interval = 0.48-0.86]), and rs1329428 (P = 5.87 x 10(-6), odds ratio = 1.83 [95% confidence interval = 1.40-2.38]). A significant difference was found in the distribution of C4B gene copy numbers in aCSC patients compared with controls (P = 0.0042). No differences could be found among the selected variants between aCSC and cCSC patients.Conclusion: Three variants in the CFH gene and copy number variations in C4B were found to be significantly associated with the risk of aCSC development. Despite the differences in clinical presentation, acute and chronic CSC may share a similar genetic predisposition based on our present analysis. Other genetic and/or nongenetic risk factors may be more influential in the differentiation toward an acute or a chronic phenotype of CSC. Show less
