Search

Alpha-synuclein gene (SNCA) polymorphisms have been associated with the common sporadic form of Parkinson's disease (PD). We searched for DNA variants at the SNCA 3' UTR through single strand conformation analysis and direct sequencing in a cohort of Spanish PD patients and controls. We have genotyped the rs356165 SNCA 3' UTR polymorphism in a total of 1,135 PD patients and 772 healthy controls from two Spanish cohorts (Asturias and Navarre). We identified six SNCA 3' UTR variants. Single nucleotide polymorphism (SNP) rs356165 was significantly associated with PD risk in the Spanish cohort (p = 0.0001; odd ratio = 1.37, 95%CI = 1.19-1.58). This SNP was also significantly associated with early age at onset of PD. Our work highlights rs356165 as an important determinant of the risk of developing PD and early age at onset and encourages future research to identify a functional effect on SNCA expression.

Recent genome-wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16-18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single-nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single-nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10(-4) ) and SNCA (rs356219; P = 5.5 × 10(-4) ) were significantly associated with Parkinson's disease. However, none of the markers in PARK16-18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome-wide association studies include effects of population structure, power, and population-specific environmental interactions. Our findings suggest that additional studies of PARK16-18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European-derived populations. © 2011 Movement Disorder Society., (Copyright © 2011 Movement Disorder Society.)

MicroRNAs are small RNA sequences that negatively regulate gene expression by binding to the 3' untranslated regions of mRNAs. MiR-133b has been implicated in Parkinson's disease (PD) by a mechanism that involves the regulation of the transcription factor PITX3. The variation in these genes could contribute to the risk of developing PD. We searched for DNA variants in miR-133 and PITX3 genes in PD patients and healthy controls from Spain. We found common DNA variants in the three miR-133 genes. Genotyping of a first set of patients (n = 777) and controls (n = 650) showed a higher frequency of homozygous for a miR-133b variant (-90 del A) in PD-patients (6/575; 1%) than in healthy controls (0/650) (P = 0.03). However, this association was not confirmed in a second set of patients (1/250; 0.4%) and controls (2/210; 1%). No common PITX3 variants were associated with PD, although a rare missense change (G32S) was found in only one patient and none of the controls. In conclusion, we report the variation in genes of a pathway that has been involved in dopaminergic neuron differentiation and survival. Our work suggests that miR-133 and PITX3 gene variants did not contribute to the risk for PD., ((c) 2010 Wiley-Liss, Inc.)

DNA variation at the FGF20 gene has been associated with Parkinson's disease (PD). In particular, SNP rs12720208 in the 3' untranslated region (3' UTR) was linked to PD-risk through a mechanism that would implicate a differential binding to microRNA-433 (miR-433). The reduction of the affinity of miR-433 to the 3' UTR would result in increased FGF20 expression and upregulation of alpha-synuclein, which could in turn promote dopaminergic neurons degeneration. We genotyped the rs12720208 SNP in a total of 512 PD patients and 258 healthy controls from Spain, and searched for miR-433 variants in the patients. We did not find significant differences in allele and genotype frequencies between patients and controls. None of the patients had miR-433 variants. In conclusion, our work did not confirm the association between rs12720208 and PD, or an effect of miR-433 variants on this disease., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction and Objectives: Influenza A is expected to have a great impact in countries in the northern hemisphere yet little has been reported about how this outbreak can affect hospital care. The aim of this study is to assess patients who demand care for flu symptoms and their outcome., Material and Methods: From the beginning of the outbreak a specific protocol was established for the care of patients with potential influenza A in admission, emergency and hospitalization ward. A nominal registry was designed with clinical and epidemiological data., Results: 1018 patients were evaluated for potential influenza A from the beginning of the outbreak until the 31(st) August, 2009. 77% of them fulfilled clinical criteria and were classified as suspected cases. Mean age was 31,7 years (SD17,2), 52% were women, 3,3% pregnant or puerperal. The admission rate was 23,4% with a global mean stay of 3,5 days, and 2,5 for the adults who were admitted to the short stay hospital unit. 2,8 % had pneumonia, two patients required admission to the intensive care unit and one of them died., Conclusions: Our data show an outbreak with mild illness, with a remarkable percentage of pneumonia but with good outcome. Despite of the high percentage of admissions, and in order to avoid the misleading attention to other patients, we believe that an assistance model based in specific units, short stay and post-discharge follow up could be suitable.