Abstract
Glutathione S-transferases (GSTs) are enzymes that included, in a wide range of detoxifying reactions by conjugation of glutathione, to electrophilic material. Polymorphisms in the genes that are responsible for GSTs affect, the function of the GSTs. GSTs play an active role in protection of cell against oxidative stress mechanism. Polymorphisms of GSTP1 at codon 105 amino acids forms GSTP1 important site for bind of hydrophobic electrophiles and the substitution of Ile/Val affect substrate specially catalytic activity of the enzyme and may correlate with reach to different diseases in human like diabetes mellitus type2 disease. Correlation between these polymorphisms and changes in the parameters file of diabetic patients has also been found, therefore, the results vary considerably among the studies. The polymerase chain reaction-restriction fragment length polymorphism was used to study GSTP1genetic polymorphism in 60 T2DM patients and 40 healthy individuals. Our results showed that presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (35.00% and 17.50.00%, respectively. Among patients there is an association between GSTP1and the risk of T2MD, both genotypes Ile/Val and Val/Val were more prevalent which result in 2.90 and 2.58 respectively risk towards T2DM .According to Hardy–Weinberg principle there was no deviation appears in the distribution of GSTP1 Alleles. GSTP1 genotypes do not have an effect on blood lipids after infection with diabetes mellitus.
Highlights
Type 2 mellitus (T2DM) represents a group of metabolic diseases characterized by hyperglycemia resulting from defects in pancreatic insulin secretion, insulin action, or both
Glutathione S-Transferases (GSTs) plays a major role as cellular antioxidant defense mechanism (Hayes et al.,2005).The glutathione S-transferase P1 (GSTP1) gene spanning approximately 2.8 kb is located at 11q13 and contains seven exons(Cowell et al.,1988 ; Kano et al.,1987).Two polymorphic sites in the coding DNA sequence of the GSTP1 gene have been identified, which are characterized by an A→G transition at nucleotide 313translating an isoleucine → valine substitution at codon 105 (Ile105 → Val105) in exon 5 and in second, a C→T transition at nucleotide 341 resulting in replacement of alanine → valine at the amino acid position 114 (Ala114 → Val114) in exon 6
Oxidative phosphorylation during anaerobic glycolysis lead to development of (ROS) .The cell in pancreases is unusually at risk for damage by pro-oxidant because it has low levels of antioxidant system .The family of GST genes have an active role in protecting cells from reactive oxygen speciese.GSTP1 causes the detoxification of products arising from oxidation of DNA
Summary
Type 2 mellitus (T2DM) represents a group of metabolic diseases characterized by hyperglycemia resulting from defects in pancreatic insulin secretion, insulin action, or both. Glutathione S-Transferases (GSTs) are the active family of phase II of antioxidant enzymes is detoxify different electrophilic materials , like environmental toxins , cancer material, chemotherapeutic material and products of DNA composed by ROS cause damage to internal compound. GSTs plays a major role as cellular antioxidant defense mechanism (Hayes et al.,2005).The glutathione S-transferase P1 (GSTP1) gene spanning approximately 2.8 kb is located at 11q13 and contains seven exons(Cowell et al.,1988 ; Kano et al.,1987).Two polymorphic sites in the coding DNA sequence of the GSTP1 gene have been identified, which are characterized by an A→G transition at nucleotide 313translating an isoleucine → valine substitution at codon 105 (Ile105 → Val105) in exon 5 and in second, a C→T transition at nucleotide 341 resulting in replacement of alanine → valine at the amino acid position 114 (Ala114 → Val114) in exon 6. GSTPI plays a central role in the inactivation of toxic and carcinogenic electrophiles (Hengstler et al.,1998) .GSTP1 single nucleotide polymorphism (SNP) lie on
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