Glutathione S-Transferase GSTM 1, Null Genotype May Be Associated With Susceptibility to Age-Related Cataract

Abstract

Background. Age-related cataract (ARC) is the leading cause of visual disability and reversible blindness all over the world. The different expressions of GST isozymes among animals may explain the variations in the cataract formation caused by oxidative stress. Objectives. In this study, we evaluated the distribution of GST gene polymorphisms in ARC patients and the possible associations between the presence of ARC and GST gene polymorphisms. Material and Methods. The epidemiological data was collected by a standard questionnaire and blood samples were obtained from 130 ARC patients and 159 healthy controls. Data about smoking habits of the groups was recorded. Real-time polymerase chain reaction-based methods were used to detect genetic polymorphisms. Results. The GSTM 1 null genotype was found to carry an increased risk for developing ARC (OR: 1.84, 95% CI: 1.13-2.99). The frequency of the GSTT 1 null genotype was not significantly different among the ARC patients and the controls (OR: 1.0, 95% CI: 0.64-1.6). The GSTP 1 Val/Val genotype was also not significantly different among the ARC patients and control groups (OR: 1.06, 95% CI: 0.50-2.23). GSTM 1 null genotype was highly frequent in non-smokers (OR: 3.25, 95% CI: 1.66-6.35) and moderately frequent in smokers (OR: 2.50, 95% CI: 1.28-4.86). Also, carrying the combined genotypes of GSTM 1 null, GSTT 1 and GSTP 1 105-Val allele was seen to have an increased risk of developing ARC (OR: 2.91, 95% CI: 1.31-6.44). Conclusions. This data may provide evidence that GSTM 1 gene polymorphisms may be associated with genetic susceptibility to develop ARC. Larger studies are warranted to verify these findings (Adv Clin Exp Med 2015, 24, 1, 113-119).

Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes

“…GST has also been described as a glaucoma associated stress marker, and increased serum GST immunoreactivity was reported in glaucoma patients. Furthermore, polymorphisms of selected GSTs such as GSTM1 and GSTT1 were shown to be associated with the onset and development of glaucoma 82 , 83 , cataract 84 , 85 , PD 86 , 87 and AD 88 .…”

Unfolded protein response is activated in aged retinas

“…The cellular mechanisms of age-related ocular disorders, such as age-related macular degeneration (AMD) [3, 4, 14, 25], diabetic retinopathy [19, 23, 41], glaucoma [1, 9, 11], and cataracts [5, 37], are tightly associated with oxidative stress, inflammation, and the unfolded protein response (UPR), suggesting cross talk between these cellular signals. Oxidative stress has been found to play a deteriorating role in aged retinas by producing reactive oxygen species (ROS) that are known to trigger different retinopathies, causing damage to the mitochondrial DNA.…”

Genetic polymorphism of glutathione s-transferase M1 (GSTM1) in patients with susceptible and resistant tuberculosis

“…The cDNAs encoded by GSTM1 and GSTM2 share a remarkable 99% sequence identity. The fact that GSTM1 and GSTM2 are physically linked suggests that the frequent deletion of the GSTM1 locus is caused by unequal crossing-over 15,16 . Furthermore, in HeLa cells, it has been confirmed that GSTM2 overexpression, following transient knockdown of GSTM1 and the absence of GSTM1 activity, may be compensated by the overexpression of GSTM2 17 .…”