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

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 - Hum. Mutat. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.

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Related in: MedlinePlus

Suppression of the CDH5 gene by steroids in vitro. A: Normalized level of Cdh5 in mouse endothelial cells shows striking down regulation of mRNA following treatment with prednisolone (Prd) at two concentrations. Expression of Cdh5 was significantly reduced in all steroid treated cultures (P < 0.05). B: Organ cultures of human RPE/choroid downregulate expression of the CDH5 gene when exposed to prednisolone. When compared with the expression levels of RLPB1, CDH5 expression in prednisolone treated cultures was suppressed by greater than fourfold compared with the control cultures (CTL; P < 0.05). In all cases, no fold change is set to 0 and error bars indicate standard deviation.
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fig03: Suppression of the CDH5 gene by steroids in vitro. A: Normalized level of Cdh5 in mouse endothelial cells shows striking down regulation of mRNA following treatment with prednisolone (Prd) at two concentrations. Expression of Cdh5 was significantly reduced in all steroid treated cultures (P < 0.05). B: Organ cultures of human RPE/choroid downregulate expression of the CDH5 gene when exposed to prednisolone. When compared with the expression levels of RLPB1, CDH5 expression in prednisolone treated cultures was suppressed by greater than fourfold compared with the control cultures (CTL; P < 0.05). In all cases, no fold change is set to 0 and error bars indicate standard deviation.

Mentions: The C166 endothelial cell line was exposed to prednisolone for 6 hr. Treatment resulted in significantly reduced Cdh5 expression (fold change >-2.5, P < 0.05) at all tested concentrations (Fig.3A) when normalized to expression of Rpl19. In contrast, treatment of C166 EC with testosterone, a steroid that has not been linked to changes in CSC incidence or severity, shows no significant change in CDH5 expression.


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

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 - Hum. Mutat. (2014)

Suppression of the CDH5 gene by steroids in vitro. A: Normalized level of Cdh5 in mouse endothelial cells shows striking down regulation of mRNA following treatment with prednisolone (Prd) at two concentrations. Expression of Cdh5 was significantly reduced in all steroid treated cultures (P < 0.05). B: Organ cultures of human RPE/choroid downregulate expression of the CDH5 gene when exposed to prednisolone. When compared with the expression levels of RLPB1, CDH5 expression in prednisolone treated cultures was suppressed by greater than fourfold compared with the control cultures (CTL; P < 0.05). In all cases, no fold change is set to 0 and error bars indicate standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215937&req=5

fig03: Suppression of the CDH5 gene by steroids in vitro. A: Normalized level of Cdh5 in mouse endothelial cells shows striking down regulation of mRNA following treatment with prednisolone (Prd) at two concentrations. Expression of Cdh5 was significantly reduced in all steroid treated cultures (P < 0.05). B: Organ cultures of human RPE/choroid downregulate expression of the CDH5 gene when exposed to prednisolone. When compared with the expression levels of RLPB1, CDH5 expression in prednisolone treated cultures was suppressed by greater than fourfold compared with the control cultures (CTL; P < 0.05). In all cases, no fold change is set to 0 and error bars indicate standard deviation.
Mentions: The C166 endothelial cell line was exposed to prednisolone for 6 hr. Treatment resulted in significantly reduced Cdh5 expression (fold change >-2.5, P < 0.05) at all tested concentrations (Fig.3A) when normalized to expression of Rpl19. In contrast, treatment of C166 EC with testosterone, a steroid that has not been linked to changes in CSC incidence or severity, shows no significant change in CDH5 expression.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Columbia University, New York City, New York.

Show MeSH
Related in: MedlinePlus