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; Inger C Munch; Arlene V Drack; Jasmine Hernandez; Suzanne Yzer; Joanna E Merriam; Allan Linneberg; Michael Larsen; Lawrence A Yannuzzi; Robert F Mullins; Rando Allikmets

doi:10.1002/humu.22551

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, Inger C Munch, Arlene V Drack, Jasmine Hernandez, Suzanne Yzer, Joanna E Merriam, Allan Linneberg, Michael Larsen, Lawrence A Yannuzzi, Robert F Mullins, Rando Allikmets

46 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Human Mutation
Vol/bind	35
Udgave nummer	7
Sider (fra-til)	859-867
Antal sider	9
ISSN	1059-7794
DOI	https://doi.org/10.1002/humu.22551
Status	Udgivet - jul. 2014

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10.1002/humu.22551

Citationsformater

Schubert, C., Pryds, A., Zeng, S., Xie, Y., Freund, K. B., Spaide, R. F., Merriam, J. C., Barbazetto, I., Slakter, J. S., Chang, S., Munch, I. C., Drack, A. V., Hernandez, J., Yzer, S., Merriam, J. E., Linneberg, A., Larsen, M., Yannuzzi, L. A., Mullins, R. F., & Allikmets, R. (2014). Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy. Human Mutation, 35(7), 859-867. https://doi.org/10.1002/humu.22551

Schubert, C, Pryds, A, Zeng, S, Xie, Y, Freund, KB, Spaide, RF, Merriam, JC, Barbazetto, I, Slakter, JS, Chang, S, Munch, IC, Drack, AV, Hernandez, J, Yzer, S, Merriam, JE, Linneberg, A , Larsen, M, Yannuzzi, LA, Mullins, RF & Allikmets, R 2014, 'Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy', Human Mutation, bind 35, nr. 7, s. 859-867. https://doi.org/10.1002/humu.22551

@article{d29f9424a80644fcafc1f3ca480285cf,

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.",

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

author = "Carl Schubert and Anders Pryds and Shemin Zeng and Yajing Xie and Freund, {K Bailey} and Spaide, {Richard F} and Merriam, {John C} and Irene Barbazetto and Slakter, {Jason S} and Stanley Chang and Munch, {Inger C} and Drack, {Arlene V} and Jasmine Hernandez and Suzanne Yzer and Merriam, {Joanna E} and Allan Linneberg and Michael Larsen and Yannuzzi, {Lawrence A} and Mullins, {Robert F} and Rando Allikmets",

note = "{\textcopyright} 2014 The Authors. *Human Mutation published by Wiley Periodicals, Inc.",

year = "2014",

month = jul,

doi = "10.1002/humu.22551",

language = "English",

volume = "35",

pages = "859--867",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "JohnWiley & Sons, Inc.",

number = "7",

}

TY - JOUR

T1 - Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy

AU - Schubert, Carl

AU - Pryds, Anders

AU - Zeng, Shemin

AU - Xie, Yajing

AU - Freund, K Bailey

AU - Spaide, Richard F

AU - Merriam, John C

AU - Barbazetto, Irene

AU - Slakter, Jason S

AU - Chang, Stanley

AU - Munch, Inger C

AU - Drack, Arlene V

AU - Hernandez, Jasmine

AU - Yzer, Suzanne

AU - Merriam, Joanna E

AU - Linneberg, Allan

AU - Larsen, Michael

AU - Yannuzzi, Lawrence A

AU - Mullins, Robert F

AU - Allikmets, Rando

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adrenal Cortex Hormones

KW - Adult

KW - Aged

KW - Alleles

KW - Animals

KW - Antigens, CD

KW - Cadherins

KW - Case-Control Studies

KW - Cell Line

KW - Central Serous Chorioretinopathy

KW - Choroid

KW - Endothelial Cells

KW - Female

KW - Gene Expression Regulation

KW - Gene Frequency

KW - Genetic Association Studies

KW - Haplotypes

KW - Humans

KW - Intercellular Junctions

KW - Linkage Disequilibrium

KW - Male

KW - Mice

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Protein Transport

KW - Young Adult

U2 - 10.1002/humu.22551

DO - 10.1002/humu.22551

M3 - Journal article

C2 - 24665005

SN - 1059-7794

VL - 35

SP - 859

EP - 867

JO - Human Mutation

JF - Human Mutation

IS - 7

ER -

Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy

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