Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus

Abstract

One of the characteristics of type 2 diabetes mellitus (T2DM) is the state of persistent oxidative stress (OS) that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS) and increases OS. Glutathione S-transferase P1 (GSTP1) is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls) were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05) but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotypes and disease approached significance (P=0.08). Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients. [Projekat Ministarstva nauke Republike Srbije, br. 175075

Evaluation of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and susceptibility to type 2 diabetes mellitus, a meta-analysis

“…The characteristics of each study were summarized in Table 1 (Tab. 1) (References in Table 1: Yalin et al, 2007[ 35 ]; Oniki et al, 2008[ 20 ]; Bid et al, 2010[ 6 ]; Tsai et al, 2011[ 33 ]; Ramprasath et al, 2011[ 21 ]; Amer et al, 2011[ 4 ]; Moasser et al, 2012[ 19 ]; Gönül et al, 2012[ 10 ]; Grubisa et al, 2013[ 11 ]; Mastana et al, 2013[ 17 ]; Vats et al, 2013[ 34 ]; Rao et al, 2014[ 22 ]; Abbasi et al, 2014[ 1 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]; Rasheed et al, 2016[ 23 ]; Ahmed and Al-Bachary, 2017[ 2 ]). The studies included in the present meta-analysis were conducted on different ethnic populations: 14 studies included a Caucasian population, 2 studies included an Asian population, and 2 studies included an African population.…”

“…Considering that GSTP1 belongs to GST superfamily and is involved in cellular detoxification and the fact that Ile105Val polymorphism may alter the GSTP1 enzyme activity (Zimniak et al, 1994[ 38 ]; Johansson et al, 1998[ 14 ]; Ryberg et al, 1997[ 24 ]; Hu et al, 1997[ 12 ]; Sundberg et al, 1998[ 31 ]), it seems that the rs1695 polymorphism may be associated with susceptibility to T2DM. During 2007 to 2017, eighteen studies investigate the association between this polymorphism and the risk of T2DM (Yalin et al, 2007[ 35 ]; Oniki et al, 2008[ 20 ]; Bid et al, 2010[ 6 ]; Tsai et al, 2011[ 33 ]; Ramprasath et al, 2011[ 21 ]; Amer et al, 2012[ 4 ]; Moasser et al, 2012[ 19 ]; Gönül et al, 2012[ 10 ]; Grubisa et al, 2013[ 11 ]; Mastana et al, 2013[ 17 ]; Vats et al, 2013[ 34 ]; Rao et al, 2014[ 22 ]; Abbasi et al, 2014[ 1 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]; Rasheed et al, 2016[ 23 ]; Ahmed and Al-Bachary, 2017[ 2 ]). However, the results of the studies are not consistent.…”

“…There was no report from America continent, Western Europe, Australia and East of Asia. Second, the sample size in some subgroup analysis was small (Yalin et al, 2007[ 35 ]; Tsai et al, 2011[ 33 ]; Grubisa et al, 2013[ 11 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]; Rasheed et al, 2016[ 23 ]; Ahmed and Al-Bachary, 2017[ 2 ]), which may increase the risk of false negatives or false positives. Third, there was no data regarding the source of control groups in studies used for meta-analysis (Moasser et al, 2012[ 19 ]; Grubisa et al, 2013[ 11 ]; Abbasi et al, 2014[ 1 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]; Rasheed et al, 2016[ 23 ]; Ahmed and Al-Bachary, 2017[ 2 ]).…”

“…The association between the Ile105Val GSTP1 polymorphism and the risk of T2DM has been investigated, but these studies yielded controversial results (Yalin et al, 2007[ 35 ]; Oniki et al, 2008[ 20 ]; Bid et al, 2010[ 6 ]; Tsai et al, 2011[ 33 ]; Ramprasath et al, 2011[ 21 ]; Amer et al, 2012[ 4 ]; Moasser et al, 2012[ 19 ]; Gönül et al, 2012[ 10 ]; Grubisa et al, 2013[ 11 ]; Mastana et al, 2013[ 17 ]; Vats et al, 2013[ 34 ]; Rao et al, 2014[ 22 ]; Abbasi et al, 2014[ 1 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]; Rasheed et al, 2016[ 23 ]; Ahmed and Al-Bachary, 2017[ 2 ]). Some studies suggested that the GSTP1 polymorphism is associated with susceptibility to T2DM (Bid et al, 2010[ 6 ]; Amer et al, 2012[ 4 ]; Mastana et al, 2013[ 17 ]; Vats et al, 2013[ 34 ]; Rao et al, 2014[ 22 ]; Zaki et al, 2015[ 36 ]; Stoian et al, 2015[ 29 ]; Mergani et al, 2016[ 18 ]), other reports, however, do not support the finding (Yalin et al, 2007[ 35 ]; Oniki et al, 2008[ 20 ]; Tsai et al, 2011[ 33 ]; Moasser et al, 2012[ 19 ]; Gönül et al, 2012[ 10 ]; Grubisa et al, 2013[ 11 ]; Abbasi et al, 2014[ 1 ]; Rasheed et al, 2016[ 23 ]). Whether GSTP1 polymorphism modifies the risk of T2DM remains uncertain, therefore the present meta-analysis was carried out.…”

Glutathione S-Transferase Gene Polymorphisms and the Development of New-Onset Diabetes After Liver Transplant

“…20 The transition of A→G at DNA nucleotide 313 (A313G) is known as the polymorphic site of the GSTP1 gene that leads to isoleucine→valine substitution at codon 105 (isoleucine [Ile] 105Val) in exon 5 during translation. 21,22 This substitution results in 3 GSTP1 genotypes, including the Ile/Ile homozygous wild type, valine/valine (Val/Val) homozygous variant, and heterozygote (Ile/Val) variant. The thermal stability and enzyme activity of GSTP1 are decreased in the variant homozygote.…”