JUN 12, 2014
This prospective study found that a mutant Glutathione S-transferase (GST) omega-1 and- 2 genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects.
GST omega-1 and -2 have a unique range of enzymatic activities, including the regeneration of ascorbate by their dehydroascorbate reductase activities. Because these enzymes could protect against oxidative damage in the lens, the authors investigated the association between GST omega-1 and -2 polymorphisms and age-related cataract in 100 cataract patients and 130 controls.
They found that homozygous carriers of GSTO1*Asp/GSTO2*Asp haplotype had a 3.4-fold increased risk of cataract development. Further analysis found that smokers and ultraviolet-exposed subjects who had at least one mutant omega-2 allele had nearly seven times the risk of cataract.
They write that these results suggest a role of inefficient ascorbate regeneration in cataract development. The importance of the antioxidant role of ascorbate in the lens is further confirmed in studies showing reduced ascorbate levels and increased dehydroascorbate in human lenses with age-related cataracts.
They also note that in addition to risk, the results may have implications in new approaches to antioxidant therapy in age-related cataract patients. GST genotype determination could be a step forward to individualization of antioxidant administration. Because susceptibility to oxidative damage differs with respect to GST genotype, it seems reasonable to assume that an individual’s GST genetic profile in addition to plausible oxidative stress biomarkers, also should be considered in optimization of form, dose and time course of antioxidant treatment.
In that context, in age-related cataractpatients with combined mutant variants of GSTO1/GSTO2 genotypes, the use of antioxidants other than ascorbate--such as the pyruvate esters--and xanthine alkaloids--such as caffeine--might be useful.