Genetic analysis of coding SNPs in blood-brain barrier transporter MDR1 in European Parkinson’s disease patients

Funke, Claudia; Soehn, Anne S.; Tomiuk, Juergen; Rieß, Olaf; Berg, Daniela

doi:10.1007/s00702-009-0196-y

Cited by 16 publications

(6 citation statements)

References 24 publications

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“…Westerlund [215] showed that a 1236C/T, but not 2677G/T/A or 3435C/T increases the risk of PD in a Swedish population. The lack of a direct effect of the 3435T is supported by Funke et al [216] and Furano et al [217]. The 3435T polymorphism, however, is implicated as a contributing risk factor in the development of Parkinson’s disease when combined with exposure to pesticides [218, 219].…”

Section: Gsh Transport In the Brain: Multidrug Resistance Proteins (Mmentioning

confidence: 99%

Glutathione metabolism and Parkinson's disease

Smeyne

2013

Free Radical Biology and Medicine

357

240

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It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease.

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Section: Gsh Transport In the Brain: Multidrug Resistance Proteins (Mmentioning

confidence: 99%

Glutathione metabolism and Parkinson's disease

Smeyne

2013

Free Radical Biology and Medicine

357

240

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“…Up to date, 5 studies have investigated the link between ABCB1 1236C/T polymorphism and the risk of PD. Among them, 3 studies [ 18 , 27 , 28 ] indicated no relationship between this polymorphism and the susceptibility to the disease based on the populations of Poland, China, and Germany. The other 2 studies [ 26 , 29 ] found the positive association of ABCB1 1236C/T variant with PD risk.…”

Section: Discussionmentioning

confidence: 99%

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

et al. 2016

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Background:Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results.Methods:Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association.Results:The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09–1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32–2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26–2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02–1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66–0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03–1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility.Conclusion:The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility.

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“…Several studies examining associations between PD and polymorphisms in the ABCB1 gene in European and Asian populations, without accounting for environmental exposures, reported inconsistent results (Funke et al, 2009; Furuno et al, 2002; Lee et al, 2004; Mizuta et al, 2006; Mizuta et al, 2008; Tan et al, 2005; Tan et al, 2004; Toda et al, 2003; Westerlund et al, 2009). An Italian hospital based case control study suggested an association between the TT genotype at rs1045642 and early onset (age<45) PD (Furuno et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…A Polish population based case control study found suggestive evidence of a protective association between the 2677G-3435C haplotype (G allele at rs2032582 and C allele at rs1045642) and PD (Tan et al, 2004). A German clinic based case control study restricted to PD cases with increased iron content in the substantia nigra, found no association between 10 SNPs in ABCB1 and PD (Funke et al, 2009). A Swedish hospital based case control study found no association with PD for either rs1045642 or rs2032582 (Westerlund et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Genetic variability in ABCB1, occupational pesticide exposure, and Parkinson’s disease

Narayan¹,

Sinsheimer²,

Paul³

et al. 2015

Environmental Research

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Background Studies suggested that variants in the ABCB1 gene encoding P-glycoprotein, a xenobiotic transporter, may increase susceptibility to pesticide exposures linked to Parkinson’s Disease (PD) risk. Objectives To investigate the joint impact of two ABCB1 polymorphisms and pesticide exposures on PD risk. Methods In a population-based case control study, we genotyped ABCB1 gene variants at rs1045642 (c.3435C/T) and rs2032582 (c.2677G/T/A) and assessed occupational exposures to organochlorine (OC) and organophosphorus (OP) pesticides based on self-reported occupational use and record-based ambient workplace exposures for 282 PD cases and 514 controls of European ancestry. We identified active ingredients in self-reported occupational use pesticides from a California database and estimated ambient workplace exposures between 1974 and 1999 employing a geographic information system together with records for state pesticide and land use. With unconditional logistic regression, we estimated marginal and joint contributions for occupational pesticide exposures and ABCB1 variants in PD. Results For occupationally exposed carriers of homozygous ABCB1 variant genotypes, we estimated odds ratios of 1.89 [95% confidence interval (CI): (0.87, 4.07)] to 3.71 [95% CI: (1.96, 7.02)], with the highest odds ratios estimated for occupationally exposed carriers of homozygous ABCB1 variant genotypes at both SNPs; but we found no multiplicative scale interactions. Conclusions This study lends support to a previous report that commonly used pesticides, specifically OCs and OPs, and variant ABCB1 genotypes at two polymorphic sites jointly increase risk of PD.

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Genetic analysis of coding SNPs in blood-brain barrier transporter MDR1 in European Parkinson’s disease patients

Cited by 16 publications

References 24 publications

Glutathione metabolism and Parkinson's disease

Glutathione metabolism and Parkinson's disease

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

Genetic variability in ABCB1, occupational pesticide exposure, and Parkinson’s disease

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