ABSTRACT
Cataract, or opacification of the lens, is one of the most common causes of loss of useful vision among Egyptians. Currently, surgery is the only approach for the treatment of cataract and the etiology of age-related changes in the lens is not fully understood. Oxidative damage and genetic factors have a major role in the development of age related cataract. Glutathione is the most abundant non-protein intracellular thiol, with multiple roles as antioxidant agent, and the glutathione S-transferases [GSTs] are group of polymorphic enzymes that are important in protection against oxidative damage, as they dethiolate protein-S-S-glutathione in the human lens. The study aimed to determine the effect of genetic polyorphisms of Glutathione S-transferases M1 and T1 on the risk of senile cataract in Egyptian population. Using a multiplex polymerase chain reaction [PCR], the GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptian patients with senile cataract and in 73 otherwise healthy control group with matched age and sex distribution. Serum GST activity, the level of Malondiableyde [a lipid peroxidation product] and the blood level of reduced glutathione [GSH] were estimated. The frequency of the GSTM1 positive individuals among the senile cataract group was significantly higher than in controls [57 vs 37%] with odds ratio 2.22 95% CI:1.08-4.573; p=0.029]. The risk among the GSTM1 positive individuals of developing senile caaract was even higher in female subjects: 68% of females were GSTM1 positive in the cataract group while only 38% of females had GSTM1 positive genotype in controls [OR=3.4; 95% CI: 1.284-9.067; p=0.012]. combination of "GSTM1 positive and GSTT1 positive" genotypes [OR = 2.16; 95% CI: 0998-4.68; P=0.049]. However the combination of "GSTM1 null, GSTT1 positive" was found to be protective from the development of senile cataract [OR=0.47; 95% CI: 0.22-0.99; p=0.045]. The study also showed significantly deceased serum level of GST and reduced glutathione [GSH] and increased level of malondialdehyde [MDA] in senile cataract patients relative to controls [p>0.001]. The present study suggests that the GSTM1 positive genotype and the combined "GSTM1 positive/GSTT1 positive" genotype may be associated with increased risk of development of senile cataract. However the "GSTM1 null/GSTT1 positive" genotype was found to be protective from the development of cataract in the Egyptian population. The correlation between polymorphic GSTs with the other cataractogenic genetic and environmental factors is highly complicated so, the study also, suggests that when evaluating the role of a particular GST gene in any disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account as much as possible. The importance to further evaluate this matter is related to the possibility of developing diagnostic tool for predicting, by non-invasive genotype analysis, the inter-individual susceptibility to the disease