Total activity of glutathione-S-transferase (GST) and polymorphisms of GSTM1 and GSTT1 genes conferring risk for the development of age related cataracts

• Published in: Experimental eye research 2012-05, Vol.98, p.67-74
• Main Authors: Sireesha, R., Laxmi, S.G. Bhagya, Mamata, M., Reddy, P. Yadagiri, Goud, P. Upender, Rao, P. Venkateshwar, Reddy, G. Bhanuprakash, Vishnupriya, S., Padma, T.
• Format: Article
• Language: English
• Subjects: 1-Chloro-2,4-dinitrobenzene; Adult; Age; age related cataracts; Aged; Aging; Catalysis; Cataract - enzymology; Cataract - genetics; Cataracts; Cortex; Data processing; Detoxification; DNA Primers - chemistry; Erythrocyte Membrane - enzymology; Erythrocytes; Eye; Eye lens; Female; Gene polymorphism; Genotype; glutathione S-transferase; Glutathione transferase; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; GSTM1; GSTM1 protein; GSTT1; GSTT1 protein; Humans; Isoenzymes - genetics; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Oxidative stress; Polymerase chain reaction; polymorphism; Polymorphism, Genetic; Prevalence; Risk Factors; Sex; Thiols; Xenobiotics
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2012.03.002

The pathogenesis of cataract is influenced by a number of factors including oxidative stress. Glutathione-S-transferase (GST) catalyses the nucleophilic addition of the thiol of GSH to electrophilic acceptors. It is important for detoxification of xenobiotics in order to protect tissues from oxidative damage. In humans, GSTT1 and GSTM1 deletion genotypes are associated with a variety of pathological conditions including certain ophthalmic diseases. In the present study, it is aimed to determine the risk of genetic polymorphisms of GSTM1 and GSTT1 isoforms of GST for developing of age related cataracts (ARCs). We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 455 patients with ARCs (108 with nuclear (NC), 105 with cortical (CC), 96 with posterior subcapsular, (PSC) and 146 with mixed type (MT)) and 205 age and sex matched controls. The GST activity in erythrocytes (RBC) and cataractous lenses was measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The frequency of GSTM1 positive individuals was significantly higher in MT cataracts followed by NC, CC and PSC types with corresponding decrease in the GSTM1 null genotypes as compared to controls. Considering the GSTT1 locus, GSTT1 null genotypes showed high frequency in patients in general as compared to controls with corresponding reduction in the GSTT1 positive genotype. The activity of GST in RBC was higher in all the types of cataracts as compared to that in controls and in cataractous lenses the mean values were slightly higher in cases of NC cataracts as compared to CC, PSC and MT. The data suggests that GSTM1 positive, GSTT1 null and double null (GSTM1 null and GSTT1 null) genotypes may confer risk for the development of ARC. The increased activity of GST found in the present study could be due to a compensatory mechanism operating in response to increased oxidative stress. ► The risk caused by the GSTM1 and GSTT1 genotypes for age related cataracts. ► Nuclear, cortical, posterior subcapsular and mixed cataracts were studied. ► Females, persons with Low BMI, late onset and non-vegetarians had higher risk. ► GSTM1 positive and GSTM1 null + GSTT1 null genotypes showed higher risk for cataracts. ► GST total activity was elevated in lenses of patients with GSTM1 null and GSTT1 null genotypes.