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Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy
Journal article   Open access   Peer reviewed

Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy

Carl Schubert, Anders Pryds, Shemin Zeng, Yajing Xie, K Bailey Freund, Richard F Spaide, John C Merriam, Irene Barbazetto, Jason S Slakter, Stanley Chang, …
Human mutation, Vol.35(7), pp.859-867
07/2014
DOI: 10.1002/humu.22551
PMCID: PMC4215937
PMID: 24665005
url
https://doi.org/10.1002/humu.22551View
Published (Version of record) Open Access

Abstract

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.
 Haplotypes Cadherins - metabolism Humans Middle Aged Male Antigens, CD - genetics Case-Control Studies Antigens, CD - metabolism Young Adult Adult Female Cadherins - genetics Choroid - drug effects Cell Line Choroid - metabolism Genetic Association Studies Endothelial Cells - metabolism Gene Frequency Adrenal Cortex Hormones - pharmacology Central Serous Chorioretinopathy - genetics Linkage Disequilibrium Protein Transport Gene Expression Regulation - drug effects Animals Adolescent Alleles Aged Mice Polymorphism, Single Nucleotide Central Serous Chorioretinopathy - metabolism Intercellular Junctions - ultrastructure Endothelial Cells - drug effects

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