**6. Conclusion**

increased risk for the occurrence of DM, and in this case, associations with some biochemical variables and laboratory data were also observed (lipid profile and HbA1c). In this study, no investigation was performed when susceptibility to DN; however, the results are clear and show that gene polymorphisms encoding GSTs are associated with the development of type

More specific studies addressing end-stage renal failure developed as a complication of DM show that this secondary complication is more common in the Asian population than in the UK population. In addition, the data are consistent and indicate that all patients of Asian ori-

A meta-analysis performed by *Saadat* (2017) [58] brought together 18 studies with a total of 5483 subjects (healthy and diabetic). Overall analysis did not indicate a significant association between *GSTP1* and type 2 DM polymorphisms. Subgroup analyzes stratified by ethnicity, year of publication, and sample size also did not reveal a significant association between

In contrast, another meta-analysis by *Orlewski* and *Orlewska* (2015) [29] reports strong evidence of association between the genes glutathione-S-transferase (GST) and diabetic nephropathy (DN) polymorphisms. The results of this study reveal that significantly increased risks were found for the occurrence of DN in individuals with *GSTM1* genotype null. However, this same study does not observe correlation between the DN and the *GSTT1* genotype null or the presence of val alleles. Despite this, the genotype combination results indicate interaction between *GSTT1* null and *GSTM1* null, suggesting a possible summation in the deficiencies of these enzymes.

These findings differ from those found in a previous study by *Fujita* et al. (2000), where no associations between DN and genotype *GSTM1* null were observed. This study was performed with two groups of Japanese patients with or without diabetic nephropathy. Statistical analyses show that the frequency of the null genotype *GSTM1* was not significantly higher in the group of patients with nephropathy than in the group of patients without nephropathy, suggesting that the null *GSTM1* genotype does not contribute to the development of DN in this

More recent studies with the Romanian population suggest that the polymorphism of the *GSTP1* Ile105Val gene was associated with the risk of developing type 2 DM, but not with the risk of developing DN. For polymorphisms in the *GSTM1* and GSTT1 genes, the results did

Studies with the Brazilian population do not indicate an association of *GSTM1* deletion polymorphism with type 2 DM susceptibility. However, the *GSTM1* null and *GSTT1* null polymorphisms reveal an influence on some observed clinical parameters (blood glucose and blood pressure). This suggests that both polymorphisms may contribute to the clinical course

On the other hand, other studies with the population of Central Brazil [61] suggest that individuals with null *GSTT1* polymorphism present an increased risk of approximately 2.9-fold for DN development. For the same population, no association of *GSTM1* null and DN was found. In this same study, the analysis of the influence of the deletion of *GSTT1* and *GSTM1*

not indicate an increased risk of developing DM or DN [30].

gin who developed end-stage renal failure had non-insulin-dependent diabetes [57].

1 DM and disease-related risk factors [31].

56 Glutathione in Health and Disease

study polymorphism and DM2 risk.

population [59].

of patients with type 2 DM [60].

Considering all the information described above, it is concluded that DM is among the main health concerns in the world. Hyperglycemia is the main characteristic of this pathology, and this unusual situation favors the imbalance between the reactive oxygen species and the antioxidant defense line produced by the individual. This condition is called oxidative stress and Glutathione and GSTs enzymes are fundamental for the reestablishment of redox homeostasis. The progression of diabetes and, consequently, prolonged exposure to this condition, favor the development of secondary complications of DM. DN is the main secondary complication that arises as result of DM.

Expression of polymorphic GST genes within several ethnic populations is remarkable. Some studies have suggested an association between genetic polymorphism of GSTs M1, T1 and P1 susceptibility to DM and its microvascular complications, and others do not. As the results are still scarce and inconsistent, more studies need to be done.
