Myrte B Breukink1, Rosa L Schellevis1, Camiel J F Boon2, Sascha Fauser3, Carel B Hoyng1, Anneke I den Hollander4, Eiko K de Jong1. 1. Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands. 2. Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany. 4. Department of Ophthalmology Radboud University Medical Center, Nijmegen, the Netherlands 4Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Abstract
PURPOSE: Chronic central serous chorioretinopathy (cCSC) has recently been associated to variants in the complement factor H gene. To further investigate the role of the complement system in cCSC, the genomic copy number variations in the complement component 4 gene (C4) were studied. METHODS: C4A and C4B copy numbers were analyzed in 197 cCSC patients and 303 healthy controls by using a Taqman copy number determination assay. Copy numbers of C4A, C4B, and the total C4 load were compared between cases and controls, by using a Fisher exact test. For this analysis Bonferroni correction was performed for three tests, and P values < 0.017 were considered to be significant. A logistic regression model was constructed to calculate the odds ratios (ORs) of each of the C4B copy numbers, using two copies as a reference. For this model P values < 0.05 were considered to be significant. RESULTS: C4B genomic copy numbers differed significantly between cCSC patients and healthy controls (P = 0.0018). Absence of C4B significantly conferred risk of cCSC (P = 0.039, OR = 2.61 [95% confidence interval (CI) = 1.05-6.52]), whereas three copies of C4B significantly decreased the risk of cCSC (P = 0.014, OR = 0.45 [95% CI = 0.23-0.85]). The C4A genomic copy numbers and total C4 load did not significantly differ between cases and controls. CONCLUSIONS: This study showed that copy numbers of C4B are significantly associated with cCSC. Carrying no copies of C4B significantly increases the risk of cCSC, whereas carrying three C4B copies is protective. These findings reinforce the hypothesis of a possible involvement of the complement system in the pathogenesis of cCSC.
PURPOSE:Chronic central serous chorioretinopathy (cCSC) has recently been associated to variants in the complement factor H gene. To further investigate the role of the complement system in cCSC, the genomic copy number variations in the complement component 4 gene (C4) were studied. METHODS: C4A and C4B copy numbers were analyzed in 197 cCSC patients and 303 healthy controls by using a Taqman copy number determination assay. Copy numbers of C4A, C4B, and the total C4 load were compared between cases and controls, by using a Fisher exact test. For this analysis Bonferroni correction was performed for three tests, and P values < 0.017 were considered to be significant. A logistic regression model was constructed to calculate the odds ratios (ORs) of each of the C4B copy numbers, using two copies as a reference. For this model P values < 0.05 were considered to be significant. RESULTS:C4B genomic copy numbers differed significantly between cCSC patients and healthy controls (P = 0.0018). Absence of C4B significantly conferred risk of cCSC (P = 0.039, OR = 2.61 [95% confidence interval (CI) = 1.05-6.52]), whereas three copies of C4B significantly decreased the risk of cCSC (P = 0.014, OR = 0.45 [95% CI = 0.23-0.85]). The C4A genomic copy numbers and total C4 load did not significantly differ between cases and controls. CONCLUSIONS: This study showed that copy numbers of C4B are significantly associated with cCSC. Carrying no copies of C4B significantly increases the risk of cCSC, whereas carrying three C4B copies is protective. These findings reinforce the hypothesis of a possible involvement of the complement system in the pathogenesis of cCSC.
Authors: Elon H C van Dijk; Rosa L Schellevis; Maaike G J M van Bergen; Myrte B Breukink; Lebriz Altay; Paula Scholz; Sascha Fauser; Onno C Meijer; Carel B Hoyng; Anneke I den Hollander; Camiel J F Boon; Eiko K de Jong Journal: JAMA Ophthalmol Date: 2017-05-01 Impact factor: 7.389
Authors: Helena M A Feenstra; Elon H C van Dijk; Thomas J van Rijssen; Roula Tsonaka; Roselie M H Diederen; Carel B Hoyng; Reinier O Schlingemann; Camiel J F Boon Journal: Graefes Arch Clin Exp Ophthalmol Date: 2022-10-07 Impact factor: 3.535
Authors: Rosa L Schellevis; Elon H C van Dijk; Myrte B Breukink; Lebriz Altay; Bjorn Bakker; Bobby P C Koeleman; Lambertus A Kiemeney; Dorine W Swinkels; Jan E E Keunen; Sascha Fauser; Carel B Hoyng; Anneke I den Hollander; Camiel J F Boon; Eiko K de Jong Journal: JAMA Ophthalmol Date: 2018-10-01 Impact factor: 7.389
Authors: Danial Mohabati; Thomas J van Rijssen; Elon Hc van Dijk; Gregorius Pm Luyten; Tom O Missotten; Carel B Hoyng; Suzanne Yzer; Camiel Jf Boon Journal: Clin Ophthalmol Date: 2018-06-07
Authors: Elon H C van Dijk; Roula Tsonaka; Ngaisah Klar-Mohamad; Diana Wouters; Aiko P J de Vries; Eiko K de Jong; Cees van Kooten; Camiel J F Boon Journal: PLoS One Date: 2017-07-03 Impact factor: 3.240