Contribution of GSTM1, GSTT1, and MTHFR polymorphisms to end-stage renal disease of unknown etiology in Mexicans

Abstract

Oxidative stress is increased in chronic kidney disease, owing to an imbalance between the oxidative and antioxidant pathways as well as a state of persistent hyperhomocysteinemia. The enzymes glutathione S-transferases (GSTs) and methylenetetrahydrofolate reductase (MTHFR) are implicated in the regulation of these pathways. This study investigates the association between polymorphisms in the Glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), and MTHFR genes and end-stage renal disease (ESRD) of unknown etiology in patients in Mexico. A Case-control study included 110 ESRD patients and 125 healthy individuals. GSTM1 and GSTT1 genotypes were determined using the multiplex polymerase chain reaction (PCR). The MTHFR C677T polymorphism was studied using a PCR/restriction fragment length polymorphism method. In ESRD patients, GSTM1 and GSTT1 null genotype frequencies were 61% and 7% respectively. GSTM1 genotype frequencies differed significantly between groups, showing that homozygous deletion of the GSTM1 gene was associated with susceptibility to ESRD of unknown etiology (P = 0.007, odds ratios = 2.05, 95% confidence interval 1.21-3.45). The MTHFR C677T polymorphism genotype and allele distributions were similar in both groups (P > 0.05), and the CT genotype was the most common genotype in both groups (45.5% and 46.6%). Our findings suggest that the GSTM1 null polymorphism appears to be associated with the ESRD of unknown etiology in patients in Mexico.

GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review

“…In our study, we found no significant difference in the frequencies of the GSTT1 and GSTM1 null genotypes among Mexican-Mestizo and Tarahumara individuals from the northwestern region of the country. In addition, we observed a high variability in the frequency of the null genotypes for GSTT1 and GSTM1 among the different geographic regions of the country, ranging from 0.03 to 0.17 for GSTT1 and from 0.22 to 0.48 for GSMT1 ( Pérez-Morales et al , 2008 , 2011 ; Sánchez-Guerra et al , 2012 ; Gutiérrez-Amavizca et al , 2013 ; Sandoval-Carrillo et al , 2014 ; García-González et al. , 2015 ; Jaramillo-Rangel et al , 2015 ).…”

“…Although studies about the distribution of GSTM1 and GSTT1 null genotypes in a Mexican-Mestizo population have been performed previously ( Pérez-Morales et al , 2008 ; Pérez-Morales et al , 2011 ; Sánchez-Guerra et al. , 2012 ; Gutiérrez-Amavizca et al , 2013 ; Sandoval-Carrillo et al , 2014 ; García-González et al , 2015 ; Jaramillo-Rangel et al , 2015 ) no reports of the prevalence of these variants in Mexican Amerindian individuals are available. Thus, the aim of this study was to determine and compare the frequencies of GSTM1 and GSTT1 null genotypes in Mexican-mestizo and Amerindian individuals (Tarahumara) from the Northwestern part of the country (State of Chihuahua) with those previously found in other regions of Mexico and around the world.…”

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

“…The GSTM1 gene belongs to a group of enzymes that is responsible for the conjugation of GSH to electrophilic xenobiotics thereby playing a key role in the biotransformation and detoxification of xenobiotics and endogenous substances [14]. It was seen in our study population that GSTM1 gene did not show Ct values in 11 out of 43 CKDu patients (25.6%), six out of 14 CKD patients (42.9%), and eight out of sixteen (50%) of the KHI.…”

“…The GSTM1 null mutation is a common polymorphism and has also been associated with the end-stage renal disease of unknown etiology in Mexican patients [14]. The GSTM1 null polymorphism individuals were also found to be more vulnerable to organochlorine pesticides leading to the development of CKDu in a study carried out in an Indian population [15].…”

“…The G6PD gene was selected as it plays a role in protection against reactive oxygen species by the production of NADPH which is required for the generation of reduced GSH, as well as due to its deficiency being linked to CKDu in another study [13]. Polymorphisms of these genes, although not in combination, have been seen in cases of CKDu and end-stage renal disease (ESRD) in Mexican [14], Indian [15], and Sri Lankan populations [13]. …”