Association of a Haplotype in the NR3C2 Gene, Encoding the Mineralocorticoid Receptor, With Chronic Central Serous Chorioretinopathy.
Chronic central serous chorioretinopathy (cCSC) is a chorioretinal disease with unknown disease etiology. The glucocorticoid receptor and the mineralocorticoid receptor, 2 glucocorticoid-binding receptors, might be involved in the pathogenesis of cCSC.



To assess the association of functional variants and haplotypes in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) genes with cCSC.



In this case-control genetic association study, 336 patients with cCSC and 1314 unaffected controls, collected at 3 university medical centers from September 1, 2009, to May 1, 2016, underwent KASP genotyping for selected variants in NR3C1 (rs56149945, rs41423247, and rs6198) and NR3C2 (rs2070951 and rs5522).



Genetic associations of 3 NR3C1 variants and 2 NR3C2 variants with cCSC.



Among the 336 patients (274 men and 62 women; mean [SD] age, 52 [10] years), after correction for multiple testing, rs2070951 in the NR3C2 gene was significantly associated with cCSC (odds ratio, 1.29; 95% CI, 1.08-1.53; P = .004). Moreover, the GA haplotype of single-nucleotide polymorphisms rs2070951 and rs5522 in NR3C2 conferred risk for cCSC (odds ratio, 1.39; 95% CI, 1.15-1.68; P = .004), whereas the CA haplotype decreased risk for cCSC (odds ratio, 0.72; 95% CI, 0.60-0.87; P < .001). Three known variants in NR3C1 that alter the activity of the glucocorticoid receptor (rs56149945, rs41423247, and rs6198) were not associated with cCSC.



In this study, the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. Since these haplotypes have previously been associated with perceived stress, this study provides a clue to bridging clinical risk factors for cCSC to underlying genetic associations.
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
Elon H C
EHC
van Dijk
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Rosa L
RL
Schellevis
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Maaike G J M
MGJM
van Bergen
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Myrte B
MB
Breukink
Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
Lebriz
L
Altay
Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
Paula
P
Scholz
Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
Sascha
S
Fauser
Division of Endocrinology and Metabolism, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands5Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Onno C
OC
Meijer
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Carel B
CB
Hoyng
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands6Department of Human Genetics, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Anneke I
AI
den Hollander
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands7Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Camiel J F
CJF
Boon
Department of Ophthalmology, Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Eiko K
EK
de Jong
D056833:Central Serous Chorioretinopathy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence
C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid