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The IUP Journal of Chemical Engineering
Role of GST M1 and T1 Polymorphism in the Development of Myopia
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Glutathione-S-Transferase is one of the enzyme systems which can detoxify several carcinogens and cytotoxic drugs. A deficiency in enzyme activity may manifest in the accumulation of toxic compounds thus resulting in several disease states. The GSTM1, GSTT1 are two genes of the GST family which exhibit null genotypes. In the present study 320 cases of Myopia were analyzed for GST gene polymorphism using multiplex PCR. The results were compared with 320 cases of age and sex matched controls. A significant difference in the genotypic distribution of GSTM1 and GSTT1 polymorphism between disease and controls has been observed. The GSTM1 genotype frequency in disease was elevated (79.36%) when compared with controls (65.31%). But the distribution of GSTT1 polymorphism did not show deviation between disease group and controls. When the data of GST was studied as combination it was observed that a significant increase of GSTM1T1 genotype was observed in disease as compared to controls. In conclusion, it was found that GSTM1 and GSTM1T1 genotype frequencies in disease was significantly elevated when compared with controls which indicates that GST enzymes not only catalyze detoxification reactions, but also catalyze reactions that result in toxic products, which may cause structural changes in the proteins present in the mullar cells. This can lead to aggregation or modification of the proteins in the mullar cells that might promote the development of myopia.

 
 

Myopia or shortsightedness is the most common human eye disease affecting 30% of the world population. Genetic and environmental factors are implicated in the onset of myopia. Environmental causes include mechanical factors, oxidative stress, nutritional factors etc. Humans vary in their ability to metabolize endogenous and exogenous compounds. Glutathione-S-Transferase is one of the enzyme systems which can detoxify several carcinogens and cytotoxic drugs. Oxidation-reduction mechanisms have special importance in many tissues, including the eye lens (Augusteyn, 1981; Spector, 1984; and Berman, 1991). Enzymes such as Catalase, Superoxide dismutase, Glutathione peroxidase, and Glutathione S-Transferase (GST) are thought to be important in the protection of the eye from oxidative damage (Spector, 1984; and Huang et al., 1993).

GSTs (EC 2.5.1.18) are a group of dimeric enzymes catalyzing the conjugation of reduced glutathione (GSH) with a broad spectrum of electrophiles and thus involved in the detoxification processes (Mannervik and Danielson, 1988). Hence, it plays a significant role in detoxification of Xenobiotics and other endogenous toxic compounds and for the protection of tissues from oxidative damage. The members of the GST gene family are placed in the multigene classes of Alpha, Mu, Pi, Kappa, Theta and Zeta on the basis of sequence identity (Meyer et al., 1991; Mannervik et al., 1992; and Board et al., 1997). Among these classes of GSTs, genetic polymorphism is well described for the GST M1, GST M3, GST T1, GST P1 and GST Z1 loci. There are three alleles at the GST M1 locus: GST M1*0, GST M1*A, and GST M1*B. The GST M1*0 is a deletion, and homozygotes for this gene express neither mRNA nor protein.

 
 

Glutathione-S-Transferase, Polymorphism, Myopia