459 research outputs found
Dopamine transporter (SLC6A3) 5' region haplotypes significantly affect transcriptional activity in vitro but are not associated with Parkinson's disease
No full textThe dopamine transporter (DAT) plays a critical role in dopaminergic neurotransmission and is also the major site of action for some drugs of abuse. The coding region of the DAT gene, SLC6A3, is well conserved, but non-coding regions are more variable, most notably a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region, which has been studied in a number of dopamine-related neurological disorders, including Parkinson's disease (PD). We aimed to characterize variation in the 5' region of SLC6A3 because little is known about the extent of variation in this region and potential consequences of such variation on gene expression. We identified multiple single nucleotide polymorphisms (SNPs) covering approximately 5000 bp 5' of exon 1 through the start of exon 2 (+ 2106). These SNPs segregated as eight haplotypes, six of which were common. These haplotypes differed significantly in activity in a reporter gene activity assay. However, we did not observe associations between common SNPs or haplotypes and PD in a case-control study of 261 incident cases and 376 age- and gender-matched unrelated controls. By contrast, we did observe a modest association of the 3' VNTR 9-repeat allele with PI) (odds ratio= 1.45; 95% confidence interval = 1.04-2.03). This association was limited to subjects 60 years of age and greater versus those less than 60 years of age. We conclude that although DAT 5' region SNPs haplotypes significantly alter in vitro transcriptional activity, they are not related to PD risk. In addition, our findings provide further evidence supporting an association of PD with the VNTR polymorphism
DNA sequence analysis of monoamine oxidase B gene coding and promoter regions in Parkinson's disease cases and unrelated controls
No full textThe allele G of the intron 13 G/A polymorphism of the monoamine oxidase B gene (MAO-B) has been associated with Parkinson's disease (PD) in several studies. Apart from a potential direct effect on splicing processes, the association of this intronic polymorphism with PD is due possibly to linkage disequilibrium with other mutations in the coding or promoter regions of the gene. We addressed this latter hypothesis by determining the DNA sequence of the entire MAO-B coding region comprising 15 exons and partial intronic sequences flanking each exon, in 33 cases with idiopathic PD and 38 unrelated controls. The promoter region of MAO-B gene up to base - 1,369 from ATG (start point of mRNA translation) was also sequenced to identify variants With potential functional effects on gene transcription. In the promoter region, a new polymorphism consisting of. a C to T single base change was detected in position -1,114 from ATG, with an allelic frequency of 3.5%, but it was not associated with PD risk. No commonly occurring ( > 10%) polymorphisms were found in the exons or the intronic sequences flanking the exons, although several rare variants were detected in the coding and promoter regions
Gender difference in the interaction of smoking and monoamine oxidase B intron 13 genotype in Parkinson's disease
No full textWe tested for gender-specific interactions between smoking and genetic polymorphisms of monoamine oxidase B (MAO-B) intron 13 (G or A allele), monoamine oxidase A (MAO-A) EcoRV (Yor N allele), and dopamine D2 recepor (DRD2) Taq1B (B1 or B2 allele) in a case-control study of 186 incident idiopathic Parkinson's disease (PD) cases and 296 age- and gender-matched controls. The odds ratios (ORs) for PD risk for ever smokers versus never smokers were 0.27 (95% CI: 0.13-0.58) for men of genotype G, and 1.26 (0.60-2.63) for men of genotype A (interaction chi2 = 8.14, P = 0.004). In contrast, for women, the OR for ever smokers versus never smokers were 0.62 (95% CI: 0.25-1.34) and 0.64 (95% CI: 0.18-2.21) for women of genotype GG/GA and AA, respectively (interaction chi2 = 0.001, P = 0.975). No interactions were detected between smoking and either MAO-A EcoRV or DRD2 Taq1B genotypes. These results suggest that a strong gender difference exists with respect to the modifying effect of MAO-B genotype on the smoking association with PD
Paraoxonase 2 (PON2) polymorphisms and Parkinson's disease
No full textOxidative stress may contribute to the pathogenesis of Parkinson's disease (PD). Paraoxonase 2 (PON2) is an ubiquitously expressed protein which displays antioxidant properties, though it does not have paraoxonase or arylesterase activity like other members of the PON gene family, such as PON1. Two coding region polymorphisms (Cys311Ser and Ala14Gly) of the PON2 gene were investigated by a newly developed method in a population-based case-control study of 179 PD patients and 293 controls. No statistically significant differences were found in the distribution of the wild type and mutant alleles between controls and PD. Similarly, no interactions between PON2 and two PON1 polymorphisms (192 and -108) were found. Polymorphisms of PON2 do not appear to be a risk factor for PD
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