In the present study, we show the effects of a single dose of Atremorine (5 g, p. o.) on plasma dopamine (DA) response and brain function in PD (n = 183) and the influence that pathogenic (<i>LRRK2</i>), metabolic (<i>CYP2D5, CYP2C9, CYP2C19, CYP3A5, NAT2</i>), transporter (<i>ABCB1</i>), pleiotropic (<i>APOE</i>), and detoxifying genes (<i>CYP1B1, GSTT1, GSTP1, GSTM1, SOD2</i>) involved in the pharmacogenetic network exerts on Atremorine-induced DA response.
The strength of the association between GSTM1 polymorphisms and PD risk was measured by odds ratios (ORs) and 95% confidence intervals (CIs) in the recessive genetic model (null genotype vs. present genotype).
Despite several recent meta-analyses showing an association between several polymorphisms in genes related with detoxification mechanisms such as cytochrome P4502D6 (CYP2D6), and glutathione transferases M1 and T1 (GSTM1, and GSTT1), data on NAT2 gene polymorphisms obtained from the current meta-analysis do not support a major association with PD risk, except in Asian populations.
Analysis according to different races found no association between GSTM1/GSTT1 polymorphisms and PD risks except for GSTM1 variant in Caucasians, which showed a weak correlation (OR 1.16 [95% CI (1.04, 1.29), I squared=6.2%, p=0.384]).
This study suggests the association between PD and previous exposure to pesticides, whose effect may be enhanced in combination with null for GSTT1/GSTM1.
We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S-transferase M1 (GSTM1) or T1 (GSTT1).
We found evidence of statistically significant gene-tobacco interaction for GSTM1, NAT2, and GSTP1, the negative association between tobacco smoking and PD being significantly enhanced in subjects expressing GSTM1-1 activity, in NAT2 fast acetylators, and in those with the GSTP1*B*C haplotype.
An association of GSTM1*0/0 with Parkinson's disease supports the hypothesis that Glutathione Transferase M1 plays a role in protecting astrocytes against toxic dopamine oxidative metabolism, and most likely by preventing toxic one-electron reduction of aminochrome.
An association of GSTM1*0/0 with Parkinson's disease supports the hypothesis that Glutathione Transferase M1 plays a role in protecting astrocytes against toxic dopamine oxidative metabolism, and most likely by preventing toxic one-electron reduction of aminochrome.
We studied genetic polymorphisms in the glutathione-S-transferase-1 (GST-1) gene region and the interleukin-1beta (IL-1beta) promoter region in patients with Parkinson's disease (PD, n = 361), as well as controls (n = 257).
No differences were observed in the distributions of GSTM1, T1 or Z1 polymorphisms between ever-smoked and never-smoked PD cases using logistic regression (all P > 0.43).
A number of other candidate gene polymorphisms including cytochrome P450 2D6, N-acetyltransferase 2, monoamine oxidase-B and glutathione-s-transferase M1 are implicated in sporadic and familial cases and may also play a minor role in the aetiology of Parkinson's disease.
We tested for associations between genotypes of GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non-deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of 214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of Caucasian ethnicity.
These results do not support the hypothesis of a possible impact of GSTM1 and GSTT1 detoxification activities in the pathogenesis of Parkinson's disease.
It was found that males with a deletion of the GSTM1 gene were more susceptible to PD and males with a deletion of the GSTT1 gene more susceptible to MND and PD, possibly implying that environmental factors which specifically target men may be involved.