5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study.

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Research Abstract Details 

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5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Abstract Text:

Samir N P Kelada,Harvey Checkoway,Sharon L R Kardia,Christopher S Carlson,Paola Costa-Mallen,David L Eaton,Jordan Firestone,Karen M Powers,Phillip D Swanson,Gary M Franklin,W T Longstreth,Terri-Smith Weller,Zahra Afsharinejad,Lucio G Costa,

The dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's disease (PD) on the basis of its critical role in dopaminergic neurotransmission. Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as eight haplotypes that differ in transcriptional activity when transfected in rat dopamine-producing cells. In the present work from a case-control study size of 293 cases and 395 controls, we employed a cladistic approach to examine gene-disease association. First, we found strong evidence of balancing selection in this region, as determined by a Tajima's D statistic of 2.97 (P<0.001). Second, we found that the eight haplotypes fit into two main clades and that diplotypes of these clades were marginally associated with PD. Then, after we classified cases and controls by the number of risk alleles, accounting for the well-known 3' region VNTR polymorphism, we found that having two or more risk alleles resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95% confidence interval (CI): 1.03-2.40]. Finally, we detected a significant interaction between occupational pesticide exposure in men and the number of risk alleles. Among pesticide-exposed subjects, the odds ratio for having two or more risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3, which affect gene expression, are associated with PD in this population and may interact with occupational pesticide exposure to increase PD risk.

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Publishing Authors By Initials

SN Kelada,H Checkoway,SL Kardia,CS Carlson,P Costa-Mallen,DL Eaton,J Firestone,KM Powers,PD Swanson,GM Franklin,WT Longstreth,TS Weller,Z Afsharinejad,LG Costa,

For similar genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research

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5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 15

Page Numbers: 3055-62

Journal Abbreviation: Hum. Mol. Genet.

ISSN: 0964-6906

DAY: 8

MONTH: 09

YEAR: 2006

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9208958

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Single Nucleotide

MESH TERMS: toxicity

Chemical & Substance for Abstract: 5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Information

Substance Name: SLC6A3 protein, human

Registry Number: 0

Grant and Affiliation Information for 5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study.

AFFILIATION: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA. keladas@mail.nih.gov

Country: England

AGENCY: United States NIEHS

GRANT: R01 ES 10750

ACRONYM: ES

MEDLINETA: Hum Mol Genet

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