Juronen E, Tasa G, Veromann S, Parts L, Tiidla A, Pulges R, Panov A, Soovere L, Koka K, Mikelsaar A V
Department of Human Biology and Genetics, Institute of General and Molecular Pathology, Estonia.
Exp Eye Res. 2000 Nov;71(5):447-52. doi: 10.1006/exer.2000.0899.
Primary open-angle glaucoma, the most common form of glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and is usually associated with elevated intraocular pressure. The etiology and genetic risk factors of primary open-angle glaucoma are mostly unknown. The aim of this study was to find out whether the polymorphism at GSTM1, GSTM3, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma, because these polymorphic enzymes are susceptibility candidates for several diseases, including such eye disease as cataract. The phenotype of GSTM1 and GSTT1 was determined by ELISA and the genotype of GSTM3 and GSTP1 was detected by polymerase chain reaction. Four hundred and fifty two Estonians (250 glaucomas and 202 controls) participated in a case-control study. A significant association of the GSTM1 polymorphism with glaucoma was observed. The frequency of the GSTM1 positive individuals among the glaucoma group was significantly higher than in controls (60 vs. 45.0%) with odds ratio of 1.83 (95% CI 1.26-2.66;P = 0.002). The risk among the GSTM1 positive individuals of developing glaucoma was even higher in the case of smoking: 62.7% of smokers were GSTM1 positive in the glaucoma group while only 33.3% of smokers had GSTM1 positive phenotype in controls (OR = 3.36; 95% CI 1.49-7.56;P = 0.012). An association with a lower level of significance was also found with the GSTM3 gene. Four% of the 250 patients with POAG were identified as carriers of the GSTM3 BB genotype, a proportion which was slightly higher than the 1.0% for the controls (OR = 4.17; 95% CI 0. 90-19.24;P = 0.144). The frequencies of the GSTT1 and GSTP1 genotypes in both groups were not statistically different. The present study suggests that the GSTM1 polymorphism may be associated with increased risk of development of primary open-angle glaucoma.
原发性开角型青光眼是最常见的青光眼类型，是一种视神经的缓慢进行性萎缩，其特征为周边视觉功能丧失，通常与眼压升高有关。原发性开角型青光眼的病因和遗传风险因素大多未知。本研究的目的是查明GSTM1、GSTM3、GSTT1和GSTP1基因座的多态性是否与青光眼易感性增加有关，因为这些多态性酶是包括白内障等眼部疾病在内的几种疾病的易感性候选因素。通过酶联免疫吸附测定法确定GSTM1和GSTT1的表型，通过聚合酶链反应检测GSTM3和GSTP1的基因型。452名爱沙尼亚人（250例青光眼患者和202名对照）参与了一项病例对照研究。观察到GSTM1多态性与青光眼之间存在显著关联。青光眼组中GSTM1阳性个体的频率显著高于对照组（60%对45.0%），优势比为1.83（95%可信区间1.26 - 2.66；P = 0.002）。在吸烟情况下，GSTM1阳性个体患青光眼的风险更高：青光眼组中62.7%的吸烟者GSTM1呈阳性，而对照组中只有33.3%的吸烟者具有GSTM1阳性表型（优势比 = 3.36；95%可信区间1.49 - 7.56；P = 0.012）。还发现与GSTM3基因存在较低显著性的关联。250例原发性开角型青光眼患者中有4%被确定为GSTM3 BB基因型携带者，这一比例略高于对照组的1.0%（优势比 = 4.17；95%可信区间0.90 - 19.24；P = 0.144）。两组中GSTT1和GSTP1基因型的频率无统计学差异。本研究表明，GSTM1多态性可能与原发性开角型青光眼发病风险增加有关。
