Genomic Copy Number Variations of the Complement Component C4B Gene Are Associated With Chronic Central Serous Chorioretinopathy

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.