The Risk of Primary Open Angle Glaucoma and Glutathione S-Transferase M1 and T1 Polymorphism among Egyptians

Purpose: Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. Genetic factors and oxidative damage have been shown to have a role in the development of primary open angle glaucoma (POAG). Glutathione Stransferases (GSTs) are a family of enzymes that inactivate xenobiotics and endogenous end products formed as secondary metabolites during oxidative stress. In humans, GSTT1 and GSTM1 deletion genotypes are associated with a variety of pathologic processes including certain ophthalmologic diseases. The aim of this study was to determine the effects of genetic polymorphisms of glutathione S transferase GSTM1 and GSTT1 on the risk of POAG in an Egyptian population. Methods: We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 32 patients with primary open angle glaucoma to 16 age, sex, and ethnically matched controls. Results: The GSTM1 positive genotype had an increased risk of developing POAG (p< 0.05, OR 4.681, 95% CI 1.190 – 18.412). The risk of glaucoma also increased significantly in subjects with a combination of GSTM1 positive and GSTT1 null genotypes (p< 0.05, OR 4.700, 95% CI 0.959 – 23.033). Conclusion: The GSTM1 positive genotype or the combination of both GSTM1 positive and GSTT1 null genotypes may be associated with the increased risk of development of POAG in the Egyptian population. The overall results indicate a possible variable association between various GSTT1 and GSTM1 genotypes and primary open angle glaucoma. Decreased GST function might interfere with the metabolism of oxidative intermediates and exacerbate the direct or indirect damaging effects of oxidative stress on the optic nerve. It is possible that these GST polymorphisms may be risk factors for primary open angle glaucoma.