An Insertion Variant in CRH Confers an Increased Risk of Central Serous Chorioretinopathy

PURPOSE. To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC). METHODS. We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts. RESULTS. The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (P-meta = 1.24 & times; 10 & minus;(11); odds ratio, 3.01; 95% confidence interval, 2.15 & ndash;4.21). The risk variant Gln52insPro decreased CRH gene expression. CONCLUSIONS. Our results implicate the hypothalamic & ndash;pituitary & ndash;adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.

Automated summary

This study identified a novel corticotropin-releasing hormone (CRH) gene variant associated with central serous chorioretinopathy (CSC). The variant was strongly associated with CSC in Chinese patients and decreased CRH gene expression. These findings implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a new rationale for therapeutic intervention.