Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China.
Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
Invest Ophthalmol Vis Sci. 2022 Aug 2;63(9):9. doi: 10.1167/iovs.63.9.9.
To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC).
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.
The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression.
Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.
鉴定与中心性浆液性脉络膜视网膜病变（CSC）相关的新型促肾上腺皮质激素释放激素（CRH）基因变异。
我们对家族性和散发性 CSC 患者及对照组进行了 CRH 的遗传研究。我们采用全外显子组测序和连锁分析，在两个有 CSC 的中国家系中发现了 CRH 基因的杂合插入变异 Gln52insPro。该变异在来自三个独立中国队列的另外 1307 例 CSC 患者和 1438 名种族匹配的对照个体中进行了评估。
该 CRH 变异在这些中国患者队列中与 CSC 强相关（Pmeta = 1.24×10-11；优势比，3.01；95%置信区间，2.15-4.21）。风险变异 Gln52insPro 降低了 CRH 基因的表达。
我们的结果提示下丘脑-垂体-肾上腺应激反应系统参与了 CSC 的发病机制，并为治疗干预提供了新的依据。
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