期刊
HUMAN MUTATION
卷 35, 期 7, 页码 859-867出版社
WILEY
DOI: 10.1002/humu.22551
关键词
CDH5; Cadherin 5; central serous chorioretinopathy; genetic association; retinal disease
资金
- Macula Vision Research Foundation
- NIH/NEI [EY017451, EY013435]
- Foundation Fighting Blindness
- Ojenforeningen
- Danish Eye Research Foundation
- Danish Eye Health Society
- Velux Foundation
- Macula Foundation
Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major cell-cell adhesion molecule in vascular endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P=0.00012; odds ratio (OR)=1.5; 95%CI [1.2;1.8], and P=0.0014; OR=0.70; 95%CI [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (P=0.0002; OR=0.61, 95% CI [0.47-0.79]). We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.
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