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Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy
Author(s) -
Schubert Carl,
Pryds Anders,
Zeng Shemin,
Xie Yajing,
Freund K. Bailey,
Spaide Richard F.,
Merriam John C.,
Barbazetto Irene,
Slakter Jason S.,
Chang Stanley,
Munch Inger C.,
Drack Arlene V.,
Hernandez Jasmine,
Yzer Suzanne,
Merriam Joanna E.,
Linneberg Allan,
Larsen Michael,
Yannuzzi Lawrence A.,
Mullins Robert F.,
Allikmets Rando
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22551
Subject(s) - biology , serous fluid , choroid , population , haplotype , corticosteroid , medicine , endocrinology , odds ratio , physiology , retina , genotype , genetics , gene , biochemistry , environmental health , neuroscience
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 ( CDH 5 ), 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 CDH 5 SNP s 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 CDH 5 , when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.