Glutathione S-transferase M1, T1, and P1 Polymorphisms and Parkinson's Disease

Kelada, Samir N.; Stapleton, Patricia L.; Farin, Federico M.; Bammler, Theo K.; Eaton, David L.; Smith‐Weller, Terri; Franklin, Gary M.; Swanson, Phillip D.; Longstreth, W. T.; Checkoway, Harvey

doi:10.1016/s0304-3940(02)01286-7

Cited by 61 publications

(48 citation statements)

References 17 publications

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“…The presence of the GSTM1 and GSTT1 alleles, as well as the GSTM1*0/*0, and GSTT1 *0/*0 genotypes, was detected by polymerase chain reaction [7,8], and a TaqMan assay was used to differentiate the GSTP1 Val/Val, GSTP1 Ile/Val, and GSTP1 Ile/Ile genotypes [8,9]. A PCR/DNA sequencing-based assay, using PCR and dye terminator-cycle sequencing, was used to detect the genetic polyadenylation variants within the 3′ flanking region of the NAT1 gene.…”

Section: Methodsmentioning

confidence: 99%

GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas

Wideroff

Vaughan

Farin

et al. 2007

Cancer Detection and Prevention

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Condensed Abstract-In a population-based case-control study in the U.S., we examined risks of histologically confirmed esophageal and gastric adenocarcinomas in relation to polymorphisms of the following genes: GSTP; GSTM1; GSTT1; NAT1; and CYP1A1. For the GSTP1 Val/Val genotype (vs. Ile/Ile), the respective ORs of esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75-4.02), 1.46 (0.57-3.73), and 1.22 (0.48-3.09), while no consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT1*10 or *11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (vs. Ile/Ile). Background-Polymorphisms in glutathione-S-transferase (GST), N-acetyltransferase (NAT) 1, and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case-control study, we examined risks in relation to polymorphisms of the following genes: GSTP; GSTM1; GSTT1; NAT1; and CYP1A1.

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Section: Methodsmentioning

confidence: 99%

GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas

Wideroff

Vaughan

Farin

et al. 2007

Cancer Detection and Prevention

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“…7 The SNP 313A/G in GSTP1 leading to amino acid replacement in the active binding site of GSTP1, decreases the catalytic activity of the enzyme. 8,9 We hypothesize that SNPs in the genes encoding for the three GST isoenzymes influences the pharmacokinetics of BU. Furthermore, this effect may be dependent on race or age of the patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of genetic polymorphisms in genes encoding GST isoenzymes on BU pharmacokinetics in adult patients undergoing hematopoietic SCT

Brink

Wessels

Hartigh

et al. 2011

Bone Marrow Transplant

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BU is used in conditioning regimens before hemopoietic SCT. High BU exposure is associated with toxicity, whereas low BU exposure leads to higher rates of therapy failure. The pharmacokinetics of BU show large interpatient variability, hypothesized to be caused by variability in BU metabolism. In this report, the effect of genetic polymorphisms in three gluthatione S-transferase genes involved in BU metabolism (hGSTA1), GSTM1 (deletion-mutation) and GSTP1 (313A/G) on the pharmacokinetics of BU in Caucasian adult patients was investigated. In all, 66 adult patients received BU as part of their conditioning regimen. After the first infusion, two serum samples were collected and measured using a HPLC assay. A one-compartment population model was used to estimate individual pharmacokinetic parameters. The genetic variants of the three glutathione S-transferase (GST) genes were determined by pyrosequencing and PCR. A reduction of 14% in BU clearance was seen for the GSTA1*B allele and an increase in BU exposure was found. No relationship was found between polymorphisms in GSTM1 and GSTP1 and BU pharmacokinetics. This study shows that an increasing number of copies of GSTA1*B allele results in a significant decrease of BU clearance.

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“…. The small number of studies that previously explored interactions between GST gene polymorphisms and smoking in PD were inconclusive and subject to limitations in study design and sample size [3,4,13]. Here we present the first population-based case control study to examine the interaction between several GST polymorphisms and smoking in PD.…”

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confidence: 97%

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

Wahner

Glatt

Bronstein

et al. 2007

Neuroscience Letters

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GSTs are a family of inducible phase II enzymes that may play a neuroprotective role in Parkinson's disease (PD). GSTs may also modify PD risk by metabolizing compounds in cigarettes, as cigarette smoking is generally found to be associated with a decrease in PD risk. Using a population-based case control study design, we examined polymorphisms of the mu, omega, pi, and theta classes of GST to elucidate the main effects and smoking-GST interactions on PD risk. From three rural California counties, we recruited 289 incident idiopathic PD cases, clinically confirmed by our study neurologist, and 270 population controls, marginally matched by age, gender, and race.We assessed main gene polymorphism associations and evaluated interactions between smoking and GST polymorphisms as departures from a multiplicative scale adjusting for age, gender, and race. We also restricted analyses to Caucasian subjects to address the potential for population stratification (n=235 cases, 220 controls).Among Caucasians, we observed a risk reduction in subjects carrying at least one variant allele for GSTO1 (OR= 0.68, 95% CI: 0.47-0.98) and also GSTO2 (OR= 0.64, 95% CI: 0.44-0.93); both genes were in strong linkage disequilibrium. No main gene effects were observed for the remaining polymorphisms. We noted a multiplicative interaction between ever having smoked regularly and GSTO1 (OR interaction = 0.55, 95% CI: 0.33-0.92) and GSTO2 (OR interaction = 0.54, 95% CI: 0.32-0.90). Results were similar when combining all races. These findings and the paucity of similar studies suggests a need for further inquiry into the association between GSTs, smoking, and PD risk. KeywordsGene-environment interaction; Glutathione-S-transferase; Parkinson's disease; SmokingThe death of dopaminergic neurons in the midbrain is a characteristic feature of Parkinson's disease (PD). Glutathione-S-transferases (GSTs), a family of inducible phase II enzymes with cytoprotective properties, are hypothesized to protect against neurodegeneration. GSTs may Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . The small number of studies that previously explored interactions between GST gene polymorphisms and smoking in PD were inconclusive and subject to limitations in study design and sample size [3,4,13]. Here we present the first population-based case control study to examine the interaction between several GST polymorphisms and smoking in PD. NIH Public AccessWe concentrated on polymorphisms in four of eight classes of cytoplasmic mammalian GSTs (mu, omega, pi, theta). These classes and their respective gene polymorphi...

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Glutathione S-transferase M1, T1, and P1 Polymorphisms and Parkinson's Disease

Cited by 61 publications

References 17 publications

GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas

GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas

Effect of genetic polymorphisms in genes encoding GST isoenzymes on BU pharmacokinetics in adult patients undergoing hematopoietic SCT

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

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