Davoudi Samaneh, Chang Victoria S, Navarro-Gomez Daniel, Stanwyck Lynn K, Sevgi Damla Duriye, Papavasileiou Evangelia, Ren Aiai, Uchiyama Eduardo, Sullivan Lynn, Lobo Ann-Marie, Papaliodis George N, Sobrin Lucia
Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA.
Department of Ophthalmology, University of Illinois-Chicago, Chicago, IL.
Mol Vis. 2018 Jan 21;24:59-74. eCollection 2018.
Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis.
Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK.
SNPs rs1040461 and rs61860052, in ras-related protein RAS23 () and annexin A11 () genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in and , were associated with uveitis as well (p=0.009 and p=0.04).
Genetic variants in and genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk.
葡萄膜炎发生于一部分结节病患者中。本研究的目的是确定先前与整体结节病相关的基因变异是否与葡萄膜炎发生风险增加有关。
招募了77名受试者，包括45例被诊断为结节病相关葡萄膜炎的患者作为病例组，以及32例无眼部受累的系统性结节病患者作为对照组。确定了先前与结节病、结节病严重程度或其他器官特异性结节病受累相关的38个单核苷酸多态性（SNP）。使用卡方检验比较眼部结节病病例与对照组的等位基因频率，并使用置换法对多个假设检验的p值进行校正。所有分析均使用PLINK进行。
分别位于ras相关蛋白RAS23（）和膜联蛋白A11（）基因中的SNP rs1040461和rs61860052与结节病相关葡萄膜炎有关。发现rs1040461的T等位基因和rs61860052的A等位基因在眼部结节病病例中更为普遍。在对多个检验假设进行校正后，这些关联仍然存在（p = 0.01和p = 0.02）。仅在对美国白人的亚组分析中，位于6号染色体主要组织相容性复合体（MHC）基因内的另外两个变异，在和中，也与葡萄膜炎有关（p = 0.009和p = 0.04）。
和基因中的基因变异与结节病相关葡萄膜炎的风险增加有关。这些基因座先前已与整体结节病风险相关。
