title: Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy.
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.
authors.affiliation: Department of Ophthalmology, Columbia University, New York City, New York.
authors.forename: Carl
authors.initials: C
authors.lastname: Schubert
authors.forename: Anders
authors.initials: A
authors.lastname: Pryds
authors.forename: Shemin
authors.initials: S
authors.lastname: Zeng
authors.forename: Yajing
authors.initials: Y
authors.lastname: Xie
authors.forename: K Bailey
authors.initials: KB
authors.lastname: Freund
authors.forename: Richard F
authors.initials: RF
authors.lastname: Spaide
authors.forename: John C
authors.initials: JC
authors.lastname: Merriam
authors.forename: Irene
authors.initials: I
authors.lastname: Barbazetto
authors.forename: Jason S
authors.initials: JS
authors.lastname: Slakter
authors.forename: Stanley
authors.initials: S
authors.lastname: Chang
authors.forename: Inger C
authors.initials: IC
authors.lastname: Munch
authors.forename: Arlene V
authors.initials: AV
authors.lastname: Drack
authors.forename: Jasmine
authors.initials: J
authors.lastname: Hernandez
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Merriam
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Yannuzzi
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D056833:Central Serous Chorioretinopathy / Q000235:genetics* / Q000378:metabolism; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007365:Intercellular Junctions / Q000648:ultrastructure; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D021381:Protein Transport; D055815:Young Adult; D000099152:Cadherin 5
chemical_list: D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5
keywords: CDH5; Cadherin 5; central serous chorioretinopathy; genetic association; retinal disease