Chronic Central Serous Chorioretinopathy Is Associated with Genetic Variants Implicated in Age-Related Macular Degeneration
Chronic Central Serous Chorioretinopathy Is Associated with Genetic Variants Implicated in Age-Related Macular Degeneration
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DOI：
10.1016/j.ophtha.2014.09.026
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发表时间：
2015-03-01
期刊：
影响因子：
13.7
通讯作者：
Boon, Camiel J. F.
中科院分区：
文献类型：
--
作者：
de Jong, Eiko K.;Breukink, Myrte B.;Boon, Camiel J. F.
目的：系统检测19个与老年性黄斑变性(AMD)相关的单核苷酸多态(SNPs)基因与慢性中心性浆液性脉络膜视网膜病变(CCSC)的相关性。设计：病例对照研究。研究对象：292名CCSC患者、1147名AMD患者和1311名对照个体。方法：我们对19个AMD相关基因座的SNPs和6个补体因子H(CFH)基因座的SNPs进行了基因分型。主要观察指标：25个AMD相关SNPs和CFH单倍型频率在CCSC患者中的等位基因频率和CFH单倍型频率以及CCSC表型细分对遗传关联的影响。结果：经Bonferroni校正后，ARMS2中的1个SNP(Rs10490924)具有统计学意义(P-未校正=0.002；优势比[OR]=0.64)。另外3个AMD基因座(CFH、TNFRSF10A、ADAMTS9)的SNP与典型的CCSC有关联的趋势。对CFH基因座的进一步分析发现，2个SNP显著增加了CCSC的风险，1个是保护性的。CFH-H3单倍型也具有保护性作用(P=0.01；OR=0.54)。使用多模式成像，197例患者被归类为典型的CCSC，52例患者在FA上有单侧异常，这些异常是CCSC的典型特征，43例患者的临床表现可以与CCSC相容，但其特征也可以提示其他黄斑疾病。结论：慢性CSC与ARMS2和CFH基因变异有关，提示CCSC和AMD在遗传和病理生理上存在重叠。有趣的是，ARMS2和CFH中导致AMD风险的等位基因可能对CCSC具有保护作用，而CFH中对AMD具有保护作用的等位基因可能对CCSC具有风险。几个SNPs的表型亚组之间的等位基因频率存在显著差异，说明正确的临床分类的重要性。(C)2015年由美国眼科学会颁发。
Purpose: In this study, single nucleotide polymorphisms (SNPs) at 19 loci, previously associated with age-related macular degeneration (AMD), were systematically tested for association in patients with chronic central serous chorioretinopathy (cCSC). In addition, we evaluated the effect of detailed phenotyping on these genetic associations.Design: Case-control study.Participants: We included 292 cCSC patients, 1147 AMD patients, and 1311 control individuals.Methods: We genotyped SNPs at 19 AMD-associated loci and 6 additional SNPs at the complement factor H (CFH) locus. Phenotyping of all patients was based on fundoscopy, spectral-domain optical coherence tomography, fluorescein angiography (FA), and indocyanine green angiography.Main Outcome Measures: We measured the allele frequencies of 25 AMD-associated SNPs and CFH haplotype frequencies in patients with cCSC and the effect of phenotypic subdivision of cCSC on genetic associations.Results: One SNP in ARMS2 (rs10490924) was significant after Bonferroni correction (P-unadjusted = 0.002; odds ratio [OR] = 0.64). The SNPs at 3 other AMD loci (CFH, TNFRSF10A, ADAMTS9) showed a trend toward association with typical cCSC. Further analysis of the CFH locus identified 2 SNPs that significantly conferred increased risk for cCSC and 1 that was protective. The CFH-H3 haplotype was also found to be protective (P = 0.01; OR = 0.54). Using multimodal imaging, 197 patients were classified as having typical cCSC, 52 patients had unilateral abnormalities on FA that were otherwise typical of cCSC, and 43 patients had a clinical picture that could be compatible with cCSC, but with features that could also indicate other macular diseases. Significant differences of the minor allele frequencies of the tested SNPs were observed between these 3 phenotypic subgroups.Conclusions: Chronic CSC is associated with genetic variants in ARMS2 and CFH, indicating a genetic and pathophysiologic overlap between cCSC and AMD. Intriguingly, alleles in ARMS2 and CFH that confer risk of AMD may be protective for cCSC, and alleles in CFH that are protective for AMD confer risk for cCSC. Significant differences in allele frequencies were found among the phenotypic subgroups for several SNPs, illustrating the importance of correct clinical classification. (C) 2015 by the American Academy of Ophthalmology.