Can Demirdöğen Birsen, Koçan Akçin Canan, Göksoy Ezgi, Yakar Gizem, Öztepe Tuğçe, Demirkaya-Budak Sinem, Oflaz Sinan
Department of Biomedical Engineering, TOBB University of Economics and Technology, Söğütözü, 06531, Ankara, Turkey.
Graefes Arch Clin Exp Ophthalmol. 2019 Oct;257(10):2257-2270. doi: 10.1007/s00417-019-04408-w. Epub 2019 Jul 10.
Pseudoexfoliation syndrome (PEX) is characterized by the accumulation of microscopic extracellular material in the anterior chamber of the eye and can lead to the development of pseudoexfoliative glaucoma (PEG) in some patients. The pathogenesis of PEX is not fully understood, and there are no objective biomarkers for its early diagnosis. Recent research has indicated that oxidative stress and inflammation might play a role in the pathophysiology of the production of pseudoexfoliation material. Therefore, in the present study, we aimed to analyze the possible association between three genetic variants of paraoxonase 1 (PON1), a well-recognized antioxidant and anti-inflammatory enzyme, and PEX/PEG.
The study population consisted of patients with PEX (n = 150), patients with PEG (n = 150), and control subjects (n = 150). PON1 -107T/C, 192Q/R, and 55L/M genotypes were determined using PCR followed by restriction fragment length polymorphism analysis. The correlation between these genetic alterations and clinical visual characteristics was also investigated.
The minor allele frequencies and genotype distributions of PON1 did not differ significantly between the PEG, PEX, and control groups. Moreover, PON1 genotypes did not significantly influence visual clinical parameters in stratification analysis. On the other hand, in correlation analysis, pattern standard deviation was significantly correlated with the -107T/C genotypes in PEX group. In addition, intraocular pressure was correlated with the 55L/M genotypes and mean deviation was correlated with the -107T/C genotypes in the control group. Furthermore, intraocular pressure was significantly inversely correlated with sex (r = - 0.116, P = 0.011) in the overall study group. Logistic regression analysis showed that having a PON1 -107TC or CC genotype is significantly associated with PEX (OR = 1.909, P = 0.020).
This study, for the first time, analyzed the relationship between PON1 genetic variants, clinical visual parameters, and PEX/PEG. The results indicated a possible role for the PON1 promoter variant in PEX.
假性剥脱综合征（PEX）的特征是眼房水中出现微观细胞外物质积聚，部分患者可发展为假性剥脱性青光眼（PEG）。PEX的发病机制尚未完全明确，且缺乏早期诊断的客观生物标志物。近期研究表明，氧化应激和炎症可能在假性剥脱物质产生的病理生理过程中起作用。因此，在本研究中，我们旨在分析对氧磷酶1（PON1）这一公认的抗氧化和抗炎酶的三种基因变异与PEX/PEG之间的可能关联。
研究人群包括PEX患者（n = 150）、PEG患者（n = 150）和对照组（n = 150）。采用聚合酶链反应（PCR）及限制性片段长度多态性分析确定PON1 -107T/C、192Q/R和55L/M基因型。还研究了这些基因改变与临床视觉特征之间的相关性。
PEG组、PEX组和对照组之间PON1的次要等位基因频率和基因型分布无显著差异。此外，在分层分析中，PON1基因型对视觉临床参数无显著影响。另一方面，在相关性分析中，PEX组的图形标准偏差与-107T/C基因型显著相关。此外，对照组中眼压与55L/M基因型相关，平均偏差与-107T/C基因型相关。此外，在整个研究组中，眼压与性别呈显著负相关（r = -0.116，P = 0.011）。逻辑回归分析显示，携带PON1 -107TC或CC基因型与PEX显著相关（比值比=1.909，P = 0.020）。
本研究首次分析了PON1基因变异、临床视觉参数与PEX/PEG之间的关系。结果表明PON1启动子变异在PEX中可能发挥作用。
