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The common variant in the GSTM1 and GSTT1 genes is related to markers of oxidative stress and inflammation in patients with coronary artery disease

Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.
Molecular Biology Reports (Impact Factor: 2.02). 10/2009; 37(1):405-10. DOI: 10.1007/s11033-009-9877-8
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ABSTRACT

Recent studies suggest that the common variant in the GSTM1 and GSTT1 genes modifies the risk of coronary artery disease (CAD), however, it is unclear whether the risk of CAD modulated by variants in the GSTM1 and GSTT1 genes was associated with alterations of indices of oxidative stress and inflammation. Our study is an attempt to provide insight into the role of GST genetic variant and markers of oxidative stress and inflammation in CAD patients. A total of 719 Chinese CAD patients were successfully genotyped. Plasma total antioxidant status (TAOS), glutathione(GSH), C-reactive protein (CRP), fibrinogen (FIB) and white blood cell count (WBC) were determined to evaluate the oxidative stress and inflammatory response. The correlations between GSTM1/GSTT1 genotypes and alterations of indices of oxidative stress and inflammation were analyzed. We found GSTM1-0/GSTT1-0 subjects had higher CRP and FIB and lower TAOS compared to patients with wild-type GSTM1/GSTT1 genes. A stepwise elevations in age, the incidences of hypertension and diabetes mellitus, levels of FIB and the number of WBC were associated with increased number of stenosed vessels. Reductions of plasma TAOS and GSH were associated with increased number of stenosed vessels. Our results suggest that GST polymorphisms maybe modify the effect on markers of oxidative stress and inflammation in Chinese CAD patients.

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    • "These include two structural variants that deleted GSTM1 and GSTT1 genes (positive/null genotype) and two nonsynonymous substitutions of GSTP1 (i.e., GSTP1*I105V, rs1695; GSTP1*I114V, rs1138272) (Bolt and Thier, 2006; Dragovic et al., 2014). The effect of these variants in influencing disease risk was evaluated with respect to different pathologic conditions: endocrinologic (Amer et al., 2011; Mastana et al., 2013), neurologic (Kiyohara et al., 2010; Piacentini et al., 2012), cardiovascular (Polimanti et al., 2011b; Tang et al., 2010), pregnancy related (Polimanti et al., 2012), infertility related (Safarinejad et al., 2010), and allergic disease related (Minelli et al., 2010; Piacentini et al., 2014). In addition to their putative involvement in different pathologic conditions, several studies have shown that these genetic variants appear at varying frequencies among human populations (Iorio et al., 2014; Polimanti et al., 2013). "
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    ABSTRACT: Objective Glutathione S-transferase (GST) variants have been widely investigated to better understand their role in several pathologic conditions. To our knowledge, no data about these genetic polymorphisms within the Turkish population are currently available. The aim of this study was to analyze GSTM1 positive/null, GSTT1 positive/null, GSTP1*I105V (rs1695), and GSTP1*A114V (rs1138272) variants in the general Turkish population, to provide information about its genetic diversity, and predisposition to GST-related diseases.Methods Genotyping was performed in 500 Turkish individuals using the Sequenom MassARRAY platform. A comparative analysis was executed using the data from the HapMap and Human Genome Diversity Projects (HGDP). Sequence variation was deeply explored using the Phase 1 data of the 1,000 Genomes Project.ResultsThe variability of GSTM1, GSTT1, and GSTP1 polymorphisms in the Turkish population was similar to that observed in Central Asian, European, and Middle Eastern populations. The high linkage disequilibrium between GSTP1*I105V and GSTP1*A114V in these populations may have a confounding effect on GSTP1 genetic association studies. In analyzing GSTM1, GSTT1, and GSTP1 sequence variation, we observed other common functional variants that may be candidates for associated studies of diseases related to GST genes (e.g., cancer, cardiovascular disease, and allergy).Conclusions This study provides novel data about GSTM1 positive/null, GSTT1 positive/null, GSTP1*I105V, and GSTP1*A114V variants in the Turkish population, and other functional variants that may affect GSTM1, GSTT1, and GSTP1 functions among worldwide populations. This information can assist in the design of future genetic association studies investigating oxidative stress-related diseases. Am. J. Hum. Biol., 2014. © 2014 Wiley Periodicals, Inc.
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    • "At the time of blood donation , a brief questionnaire that ascertained age, history of cancers, cataract, and asthma was completed. We excluded patients and control subjects with cataract or past history of cataract surgery, asthma, past history of malignancy (treated or on treatment), cardiovascular disease that on medication and known cases of glaucoma, because these traits were associated with GSTM1 and/or GSTT1 polymorphisms (Harada et al., 46 1992; Wilson et al., 2000; Saadat et al., 2004a, b; Saadat and Farvardine-Jahromi, 2006; Saadat, 2006, 2007; Unal et al., 2007; Wang et al., 2008; Tang et al., 2010). A woman with at least one first-degree relative with PE or own history of PE is considered to have a positive family his- tory. "
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    ABSTRACT: The objective of the present hospital-based case-control study was to assess the association between glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphisms and susceptibility to pre-eclampsia (PE) in Shiraz (Fars province, southern Iran). A total of 200 healthy pregnant women and 151 pre-eclamptic women were included. The healthy control group was frequency matched with the age of the pre-eclamptic women. Control women had neither PE in current pregnancy nor history of pregnancies with PE previously. The genotypes of GSTT1 and GSTM1 polymorphisms were determined using a PCR-based method. Neither GSTM1 null genotype (OR=1.07, 95 % CI: 0.70-1.64, P=0.736) nor GSTT1 null genotype (OR=0.73, 95 % CI: 0.44-1.21, P=0.233) was associated with risk of PE. Association between combination genotypes and risk of PE was not significant. When family history was entered as a covariate in analysis, adjusted ORs revealed that neither GSTM1 nor GSTT1 polymorphisms was associated with risk of PE. For meta-analysis, we identified 5 eligible studies, including 1217 subjects (515 patients, and 702 healthy controls) in relation to the study polymorphisms and risk of PE. Our present meta-analysis indicated that there neither GSTM1 (OR=0.99, 95 % CI: 0.78-1.25, P=0.955) nor GSTT1 polymorphisms (OR=0.85, 95 % CI: 0.66-1.10, P=0.223) was associated with susceptibility to PE. Taken together it seems that the polymorphisms of GSTM1 and GSTT1 are not risk factors for PE. Further investigations adjusting for confounding factors are needed to confirm the present findings.
    Full-text · Article · May 2011
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    ABSTRACT: The present study was done to determine the modulation effect(s) of polymorphisms of XRCC1, GSTM1, and GSTT1 on concentration of serum testosterone in females exposed to natural sour gas. Also we examine whether chronic exposure to natural gas containing sulfur compounds act as natural selection force on XRCC1 polymorphisms. The present study was performed on 68 healthy unrelated female students living in polluted areas of MIS. Also for investigating the effect of natural selection on XRCC1 polymorphism, a study was performed on two groups of healthy individuals of MIS citizens. The first and second groups including 94 (age range 30-85 years) and 187 individuals (age range 5-20 years), respectively. First and second groups were born and were not born in contaminated areas of the MIS, respectively. There was no significant difference between genotypes of XRCC1 for concentration of serum testosterone. Although GSTT1-null genotype had higher level of serum testosterone in comparison with the present genotype (t=2.392, df=66, P=0.023), a borderline difference between genotypes of GSTM1 for serum testosterone was observed (t=1.928, df=66, P=0.058). Analysis of variance revealed significant difference between combination genotypes of GSTM1 and GSTT1 for serum testosterone (F=4.167; df=3, 64; P=0.009). The Duncan post hoc test indicated that the combination genotype of "present GSTM1/null GSTT1" had significant higher level of testosterone. There is no evidence that XRCC1 polymorphisms have advantage/disadvantage when population exposed to natural sour gas. The polymorphisms of GSTM1 and GSTT1 modulate serum testosterone concentration in young females exposed to natural sour gas.
    No preview · Article · Mar 2010 · Molecular Biology Reports
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