Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson’s disease

Deng, Yifu; Newman, Beth; Dunne, Michael P.; Silburn, Peter A.; Mellick, George D.

doi:10.1016/j.neulet.2004.05.061

Cited by 66 publications

(49 citation statements)

References 19 publications

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“…A standard questionnaire was completed to obtain detailed epidemiological information including smoking behavior. Subjects were considered smokers if they had ever smoked at least one cigarette per day for a period of a year or more [Deng et al, 2004]. Controls of Caucasian ancestry were a combination of spouses (37%) and electoral roll volunteers who underwent the same data collection procedures and were excluded if screening responses suggested any possibility of movement or cognitive disorders.…”

Section: Case Recruitment and Phenotypingmentioning

confidence: 99%

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

Sutherland

Mellick

Newman

et al. 2008

American J of Med Genetics Pt B

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Idiopathic Parkinson's disease is a common movement disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is postulated to involve complex interactions between genetic susceptibility and environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of human chromosome 11 is a gene rich region expressing several proteins important for dopamine neuron homeostasis. We used a haplotyping approach to determine whether common genetic variation in the IGF2-INS-TH cluster influences the risk of idiopathic Parkinson's disease in a Caucasian case-control group recruited from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689 and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and gender-matched controls. Eight common haplotypes accounted for 91% of the genetic variation in our control group and one haplotype, IGF2-INS-TH*6, was significantly under-represented among the cases with idiopathic Parkinson's disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the individual polymorphisms showed that the IGF2-rs680 alternate 'A' allele accounted for the majority of the protective effect. Our findings suggest that common genetic variants in the IGF2-INS-TH cluster modify susceptibility to idiopathic Parkinson's disease.

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Section: Case Recruitment and Phenotypingmentioning

confidence: 99%

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

Sutherland

Mellick

Newman

et al. 2008

American J of Med Genetics Pt B

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“…The two previous studies that addressed the association between GSTM1 and cigarette smoking have presented inconclusive results [3,4]. An early study of 100 PD cases and 200 controls reported that the protective effect of cigarette smoking was lost for patients with the GSTM1 deletion [4].…”

Section: Nih Public Accessmentioning

confidence: 99%

“…. 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%

“…An early study of 100 PD cases and 200 controls reported that the protective effect of cigarette smoking was lost for patients with the GSTM1 deletion [4]. Deng used a case-only approach to examine GSTM1 and reported no departure from multiplicative interaction between smoking and GSTM1 [3]. The GSTM1 null genotype expresses no enzyme activity; one could speculate that the loss of enzyme activity may enhance the protective effect conferred by a metabolite of cigarette smoke that is not metabolized due to lack of this enzyme.…”

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confidence: 99%

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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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“…Ambiguous or inconsistent samples were repeated in duplicate. For some samples, whole-genome amplification was carried out with the GenomiPhi kit (GE-Amersham, Piscataway, NJ) using the manufacturer's protocol.Polymorphisms analyzed, all by published methods [Inskip et al, 1995;Chen et al, 1996;Menegon et al, 1998;Blackburn et al, 2000;Kelada et al, 2003;Deng et al, 2004], were: GSTM1 null, GSTM3 intron 6 3-bp deletion, GSTT1 null, GSTP1 Ile105Val, GSTP1 Ala114Val, GSTZ1 Lys32Glu, and GSTZ1 Arg42Gly.As our model posits a loss-of-function mechanism for an enzyme system, we compared subjects who were homozygous for each variant with those who carry one or two wild-type alleles. For the GSTP1 and GSTZ1 SNPs, we also assessed each conventionally defined [Kelada et al, 2003;Deng et al, 2004] haplotype as in homozygous and heterozygous states for relation to OA.…”

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Glutathione S‐transferase polymorphisms and onset age in α‐synuclein A53T mutant Parkinson's disease

Golbe¹,

Iorio

Μarkopoulou

et al. 2006

American J of Med Genetics Pt B

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Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has detoxification and antioxidative functions. To screen genetic variations in GST for an effect on the onset age (OA) of PD, we typed seven common genetic polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1) mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that of idiopathic PD. Our allelic analysis showed that the subjects homozygous for the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years, n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs. 46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined, both results lose statistical significance. Nevertheless, our results suggest that further investigation in GSTP1 variants and PD pathogenesis is warranted in sporadic PD and that a search for toxins that accelerate PD OA should pay particular attention to GST-P1 substrates.

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Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson’s disease

Cited by 66 publications

References 19 publications

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

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

Glutathione S‐transferase polymorphisms and onset age in α‐synuclein A53T mutant Parkinson's disease

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